Inflammation, immune dysfunction and viral disease: could micro- and nanoplastics be the missing link?

Introduction

Microplastic (MPs) pollution has emerged as a critical environmental and biomedical concern due to its pervasive presence in terrestrial, aquatic, and atmospheric compartments. MPs originate either from the degradation of larger plastic debris through physical, chemical, and biological processes or as primary microplastics intentionally manufactured for industrial and consumer applications, such as cosmetics and synthetic textiles (1). Chemical stability, and resistance to biodegradation enable their accumulation in diverse environmental matrices, including marine sediments, freshwater systems, soils, and even the human food chain and bloodstream (2, 3).

Beyond their chemical persistence, MPs function as novel ecological scaffolds that redefine the interconnectivity between environmental health and human medicine. For instance, MPs readily interact with heavy metals, persistent organic pollutants, and microbial pathogens, thereby amplifying their ecological and health risks (4). Under the One Health paradigm, the degradation of aquatic ecosystems—the primary sink for plastic pollution—serves as the initial stage for pathobiological interactions (5, 6). In these environments, MPs act as selective substrates that concentrate microorganisms and viral populations (5, 7, 8), potentially facilitating zoonotic spillover by bridging the gap between wildlife reservoirs and human exposure routes. Consequently, the ‘plastisphere’ does not merely represent an environmental hazard but a critical interface where ecological imbalance directly translates into heightened susceptibility to viral diseases in human populations.

Recent research has begun to uncover that the interaction between MPs and viruses extends beyond simple co-occurrence in contaminated environments (8, 9). The physicochemical characteristics of MPs—such as polymer type, surface charge, and hydrophobicity—govern viral adsorption and retention, primarily through electrostatic, hydrophobic, and Van der Waals interactions (10). These associations may shield viruses from environmental degradation, prolong their infectivity, and facilitate their transmission to new hosts (9, 11). The detection of MPs in drinking water, atmospheric aerosols, and agricultural soils further highlights the potential for human exposure to virus-laden plastic particles via inhalation, ingestion, or dermal contact (12–14). Beyond serving as environmental reservoirs, MPs interact with biological tissues, inducing structural and functional alterations that compromise epithelial barriers, disturb cellular homeostasis, and may facilitate viral entry (11, 15, 16). MPs can also trigger oxidative stress and inflammatory responses, generating a pro-inflammatory microenvironment that favors viral replication and dissemination, especially within the respiratory and gastrointestinal tracts—key portals of MPs exposure (17, 18). Parallel studies demonstrate that MPs disrupt immune regulation by activating innate immune sensors (e.g., Toll-like receptors (TLRs), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome) and promoting the release of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and Tumor necrosis factor alpha (TNF-α) (19, 20). This persistent activation contributes to chronic inflammation, immune exhaustion, and tissue damage. Furthermore, MPs have been associated with immunotoxic effects, including suppression of antiviral signaling (e.g., Retinoic acid-inducible gene I (RIG-I)/IFN regulatory factor 3 (IRF3) and Stimulator of Interferon Genes (STING) pathways), thereby weakening host defenses and potentially enabling viral persistence (20–22).

Collectively, these findings suggest that MPs are not inert environmental pollutants but biologically active particles capable of modulating inflammation and influencing viral pathogenesis. This review synthesizes current evidence on the multifaceted relationship between MPs, immune dysfunction, and viral disease, focusing on how MPs may act as viral vectors, amplify inflammatory responses, and exacerbate the course of viral infections. By integrating environmental, molecular, and immunological perspectives, we propose that microplastics represent a missing link between environmental contamination, chronic inflammation, and the severity of viral diseases—highlighting the urgent need for interdisciplinary research to assess their impact on global health.

Microplastics: physico-chemical features and exposure routes

Microplastics are defined as ubiquitous synthetic particles characterized by a diameter of less than 5 mm (23, 24). MPs occur in various forms, including textile microfibers, fragments, industrial pellets, foam, and microbeads (25). In terms of size, plastics are classified into different categories: nanoplastics (NPs) (1–1000 nm and <20 μm), microplastics (1–5 mm), and even larger sizes, which are not discussed here (26, 27).

MP/NPs originate from a wide range of sources and can be classified into two main categories: primary and secondary. Primary MPs are intentionally manufactured at micro-scale for specific applications, such as cosmetic microbeads, industrial abrasives, and synthetic textiles, as well as particles generated from tire-and-road wear. Secondary MPs arise from the environmental fragmentation of larger plastic objects, such as bottles, bags, fishing nets, and other plastic debris that degrade in the environment due to sunlight radiation, mechanical weathering, and wave action. This degradation process generates microplastic particles that can persist in the environment for centuries (23, 28). Among the most used plastic polymers are polypropylene (PP), polyethylene (PE), polyethylene terephthalate (PET), polycarbonate (PC), polyvinyl chloride (PVC), polystyrene (PS), and nylon (29).

Humans are exposed to MPs primarily through ingestion, inhalation, and dermal contact (30). Ingestion is the most relevant and well-documented pathway, given the presence of MPs in a wide variety of foods —particularly in marine products such as fish and shellfish—as well as in drinking water. In addition, processed foods, table salt, and honey have also been reported as potential sources (31, 32). Inhalation constitutes another critical route, especially in urban and industrial environments, where airborne MPs -primarily derived from synthetic textiles and tire erosion- can reach the pulmonary alveoli and trigger inflammatory effects (33). Dermal exposure, although less studied, occurs through contact with cosmetic products, exfoliants, and synthetic textiles that may release MPs onto the skin; however, cutaneous absorption is still considered limited compared with other exposure routes (34).

Recent evidence has demonstrated MPs’ ability to cross physiological barriers and accumulate in human tissues. MPs have been identified in a diverse range of human tissues and fluids, including the lungs (35), feces (31), the large and small intestine (35), placenta (36), blood (37), liver (38), urine (39), and reproductive fluids such as ovarian follicular fluid (40) and semen (41), indicating systemic distribution and bioaccumulation. An alarming finding is that the recent detection of MPs in human brain tissue provides compelling evidence that these particles can access the central nervous system (42). While this finding raises the possibility of blood–brain barrier translocation, the precise mechanisms—including the role of particle size, surface charge, and persistence—remain to be elucidated. This systemic infiltration raises urgent questions regarding the long-term effects on human health.

A critical structural attribute of MPs is their high surface adsorption capacity, which facilitates the formation of a ‘chemical corona.’ This phenomenon enables MPs to serve as vectors for a wide array of hazardous xenobiotics, including environmental pollutants and viral particles, with implications discussed in the following sections.

Impact of microplastics on the immune system

The inflammatory response is an essential biological reaction of the immune system to external insults, such as pathogenic microorganisms, toxins, or tissue injury. This response is characterized by a sequence of physiological processes, including vasodilation, increased vascular permeability, and the infiltration of immune cells into the affected site. A crucial aspect of this inflammatory cascade is the production of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and IL-6, which function as signaling molecules to recruit and activate additional immune cell populations (43).

While MPs have traditionally been studied within the framework of ecotoxicology, recent evidence reveals that they also exert direct effects on the immune system. Their diminished size, surface charge, and polymeric composition enable them to bypass epithelial barriers, accumulate in immunologically active tissues, and trigger inflammatory responses. Elucidating the cellular and molecular mechanisms through which MPs induce immunotoxicity—including oxidative stress, inflammasome activation, and cytokine dysregulation—is fundamental to contextualizing their role as potential cofactors in both inflammatory and infectious diseases.

Biodistribution and cellular uptake: from the epithelial barrier to immune cells

MP/NPs, like other particulate matter, can cross epithelial membranes and reach underlying tissues, where they interact with resident immune cells, thereby triggering cellular stress signaling pathways (44).

The kinetics of this translocation have been characterized in human respiratory (A549, BEAS-2B) and intestinal (Caco-2) epithelial cell lines. Confocal microscopy studies demonstrate that PS particles can translocate across epithelial layers within a 5-to-24-hour window, with efficiency being dependent on particle size and ambient flow conditions (44). Once in contact with cells, internalization is mediated through phagocytosis, micropinocytosis, or even clathrin- or caveolin-dependent endocytosis. The selection of these specific uptake routes is dictated by the particles’ physicochemical properties (45)—primarily size and surface charge—and are further modulated by environmental exposure conditions in both epithelial cells and macrophages (46).

Despite robust cellular uptake observed in vitro, in vivo evidence in rodent models suggests relatively low acute bioavailability, with intestinal absorption rates estimated at 0.04%-0.3% (47). However, these low percentages must be contextualized within the framework of chronic exposure. The ubiquity of MPs in air, water, and food ensures a continuous, lifelong intake. Consequently, even low-efficiency translocation may result in progressive systemic accumulation over time, thereby increasing the risk of immune dysfunction and adverse health outcomes.

Barrier damage and inflammatory priming in the epithelium

Within the intestinal epithelium, MPs disrupt tight junctions (ZO-1, occludin, claudins). This structural failure increases permeability through a reactive oxygen species (ROS)→ (nuclear factor kappa B) NF-κB→NLRP3→IL-1β→MLCK axis, a mechanism characterized in Caco-2 cells exposed to polystyrene microplastics (PS-MPs) (48). The toxicological impact of these particles is significantly modulated by the “chemical corona.” For instance, PS-MPs with adsorbed nonylphenol have been shown to exacerbate oxidative stress and inflammation, leading to impairments in barrier function, highlighting the critical role of the chemical corona in defining the pathogenicity of environmentally “aged” or realistic MPs (49). The physiological relevance of these findings is corroborated by in vivo evidence in zebrafish larvae, where polystyrene nanoplastics (PS-NPs) induce intestinal damage and structural disorganization, with translational relevance given the conservation of response pathways across vertebrates (50). At the histological level in mice, exposure to PS-MPs alters intestinal ultrastructure and downregulates the expression of tight junction–related genes, consistent with loss of epithelial integrity as evidenced by microscopy and qPCR analyses (51). More broadly, gut microbiota dysbiosis has been linked to altered inflammatory tone, epithelial barrier dysfunction, and immune-metabolic regulation, supporting the relevance of microbiota-centered mechanisms in environmentally induced immune perturbation (52).

Activation of the NLRP3 inflammasome and immune dysfunction

When MP/NPs reach the biological interface or are internalized, they are recognized by innate immune sensors as either pathogen-associated or danger-associated molecular patterns (PAMPs and DAMPs). This interaction can significantly alter the organism’s inflammatory capacity, with activation of the NLRP3 inflammasome among the central mechanisms involved (53–55).

At the cellular level, chronic exposure to MPs may lead to persistent immune stimulation, an imbalance between effector and regulatory cells, and eventually, immune exhaustion. In human monocytic lines (THP-1), diverse MP/NPs induce NLRP3 activation and increased IL-1β production, a mechanism validated in NLRP3-deficient cell lines (56). Likewise, in THP-1 cells and murine lung epithelial cells (MLE-12), amino-modified PS-NPs (50–100 nm) activate the NLRP3/caspase-1 pathway. This activation promotes IL-1β maturation and gasdermin D (GSDMD) cleavage, thereby triggering pyroptosis (56) (a highly inflammatory form of programmed cell death). In human PBMC-derived macrophages, MP/NPs exposure alters cell viability, inflammatory profiles, and effector functions (including phagocytosis and ROS production) (57). Consistently, high MPs uptake in murine macrophages correlates with cellular stress and impaired proliferation. The resulting cytotoxicity depends on concentration, particle size, and the specific cell line, reflecting heterogeneity in biological susceptibility (58).

In intestinal and respiratory epithelium, a ROS → NF-κB → NLRP3 axis links oxidative stress to pyroptosis and IL-1β production (48). Complementary studies in BEAS-2B bronchial epithelial cells indicate that PS-MPs induce autophagic cell death, further promoting the release of pro-inflammatory DAMPs (59). The effects of MPs depend on their size and surface characteristics; while ~100 nm PS-NPs stimulate ROS generation and NLRP3-mediated signaling in murine hepatocytes (60), larger micrometer-sized particles have been observed to decrease NLRP3 expression in human embryonic kidney cells HEK293 cells (61), highlighting how particle size dictates the inflammatory response.

In vivo models, including mice, rats, birds, and fish, confirm that MPs exposure induces inflammasome activation and NLRP3/caspase-1–mediated pyroptosis (17, 62–64). In rats, this activation is associated with hepatic and ovarian inflammation (64, 65), accompanied by a disruption in the Th17/Treg balance and elevated serum IL-1 levels (66). In aquatic and avian models, NLRP3 activation correlates with intestinal and cardiac injury (67–69). Notably, these toxicological effects may be intensified under combined scenarios: for instance, co-exposure to PS-NPs and arsenic in mice activates NLRP3/caspase-1 and triggers hepatic pyroptosis (70).

In aquatic organisms and invertebrates, MPs also induce inflammation and intestinal dysbiosis. In mussels, zebrafish, and nematodes, immunological alterations, disruption of phagocytosis, increased ROS production, and activation of endoplasmic reticulum stress have been observed, compromising cellular homeostasis (67–69, 71–74). Oxidative stress consistently emerges as the primary upstream event following MP phagocytosis across all biological models (63–65, 75). Furthermore, host factors such as biological sex modulate these outcomes; carboxylated PS-NPs have been shown to upregulate NLRP3 in the female murine hippocampus, whereas they exert the opposite effect in males (76).

In the human context, MPs have been detected in lymph nodes adjacent to prostheses, where they are associated with chronic macrophage activation (77). Common polymers like Acrylonitrile Butadiene Styrene (ABS) and Polyvinyl Chloride (PVC) also trigger the production of IL-6 and TNF-α in immune cells (78). At the same time, NPs have been linked to protein conformational changes and genotoxic effects in vitro (79).

Given the multifaceted inflammatory cascades associated with MPs exposure, an important direction for future research is their role in ‘trained immunity’—a form of innate immune memory. It is imperative to evaluate how MP-induced epigenetic reprogramming and metabolic shifts fundamentally alter the immunological landscape. Such modifications could condition the magnitude and efficacy of host responses against subsequent viral challenges, potentially leading to maladaptive immune states that heighten susceptibility to infection and exacerbate disease severity.

Interaction between microplastics and viruses: evidence of their role as environmental vectors

The physicochemical properties that enable MP/NPs to interact with cellular membranes also facilitate their high affinity for viral particles in the environment. This binding is driven by an interplay of non-specific physicochemical forces, whose strength and nature depend on the polymer type, surface charge, hydrophobicity, particle size, surface roughness, and environmental aging, particularly that induced by ultraviolet radiation (80, 81). Besides, environmental or ultraviolet (UV) radiation–induced aging introduces polar functional groups (–OH, –COOH) on the plastic surface, thereby strengthening hydrophobic interactions and hydrogen bonding between the viral capsid and aged MPs (82). As a result, MPs can function as solid matrices that promote viral adsorption, transport, and persistence, acting as environmental reservoirs and vectors that may prolong viral stability and infectivity in both aquatic and terrestrial ecosystems (11). Viral particles adhere to MP/NPs through a combination of electrostatic, hydrophobic, and van der Waals forces, as well as π–π interactions in polymers containing aromatic rings, such as PS (80, 81). Experimental evidence highlights the efficiency of this “Trojan horse” mechanism. For instance, up to 98.6% of bacteriophage T4 particles adsorb onto PS-MPs, driven primarily by electrostatic complementarity (11). Consistently, the sorption of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) onto laundry-derived microfibers is governed by a synergy of electrostatic and hydrophobic forces, which provides mechanical protection to the virion and reduces its degradation rate (8), thereby increasing the likelihood of indirect transmission. Beyond simple adsorption, MP/NPs may act as “delivery platforms” that facilitate viral persistence, transport, and host interaction through several complementary mechanisms. First, plastic particles can concentrate virions on their surface, thereby increasing the local density of viral particles and enhancing the probability of contact with susceptible cells or epithelial interfaces (8, 9, 11, 82–84). Second, adsorption onto MP/NP surfaces or onto the associated chemical/biomolecular corona may protect virions from environmental stressors, including dilution, enzymatic degradation, temperature shifts, and UV-mediated inactivation, potentially prolonging viral persistence in aquatic, terrestrial, or biological matrices (8, 9, 11, 82, 83). Third, MP/NPs may function as mobile carriers that support viral transport across environmental compartments and contaminated interfaces, particularly when embedded within biofilms or the plastisphere (11, 14, 85, 86). Fourth, once in contact with host barriers, MP/NPs may indirectly facilitate viral infection by disrupting epithelial integrity, altering tight junction expression, inducing oxidative stress, and promoting inflammatory priming, all of which may increase tissue vulnerability to infection or amplify virus-induced immunopathology (17, 18, 20, 48, 51). Finally, emerging evidence suggests that MP/NPs may affect intracellular processes involved in viral entry and dissemination, including suppression of antiviral signaling pathways such as RIG-I/IRF3 and STING, as well as migrasome-mediated viral spread (87–89). Collectively, these mechanisms support the concept that MP/NPs can act not only as environmental reservoirs but also as biophysical and immunological cofactors of viral infection. However, most evidence remains experimental, and the relevance of these mechanisms to human viral transmission and disease severity requires further validation.

Viral stability on plastic surfaces has been confirmed across diverse experimental models. Avian influenza virus H9N2 remained detectable for up to 14 days on PE, PS, and PET (9), while Hepatitis E virus (HEV) retains infectivity for up to 8 weeks on plastic surfaces, significantly longer than on natural materials like wood or ceramic (90). Similarly, human coronavirus 229E preserved its infectivity for at least 5 days on polytetrafluoroethylene (PTFE) and PVC surfaces (91). More recently, it was demonstrated that MPs not only allow SARS-CoV-2 adsorption but also increase its infectivity in vitro in human cells, an effect associated with the activation of inflammatory markers such as TNF-α, IL-8, and caspase-3 (18). Li et al. demonstrated the direct adsorption of Zika virus particles onto PS-MP using electron microscopy and infectivity assays. The authors showed that MPs act as collector surfaces that retain virions, thereby altering their distribution and potentially their ability to contact susceptible cells. This finding broadens the spectrum of viruses with affinity for MPs to include zoonotic agents of high public health relevance, confirming that this phenomenon is not restricted to enteric or environmental viruses (84).

The concept of the “plastisphere”—a microbial biofilm that colonizes floating plastic debris in aquatic environments—adds a new ecological dimension to this interaction. In marine environments, MPs have been identified as complex microhabitats harboring diverse viral orders (Herpesvirales, Caudovirales) and pathogens such as the White Spot Syndrome Virus (WSSV), often co-existing with potentially pathogenic bacteria like Vibrio spp (85). In freshwater environments, human adenoviruses and noroviruses have been detected on submerged plastics, together with viable bacteria such as E. coli and Listeria monocytogenes (86). After only a few weeks of exposure, these surfaces exhibited diverse and seasonally variable microbial colonization, reinforcing their role as dynamic reservoirs of pathogenic microorganisms. The presence of a biofilm appears to confer additional stability to both enveloped (e.g., bacteriophage Phi6) and non-enveloped (e.g., Rotavirus SA11) viruses, reinforcing the role of MPs as dynamic, seasonally variable reservoirs that protect pathogens from environmental inactivation (18). This coexistence suggests that MPs are not merely inert substrates but rather complex microhabitats that can protect viruses from inactivation and promote synergistic interactions with microbial communities.

The environmental trajectory of MP-virus complexes underscores the necessity of a One Health approach to infectious disease surveillance. Aquatic systems act as epicenters where the intersection of high microplastic density and diverse viral loads facilitates the emergence of ‘plastisphere-associated’ pathogens. By providing long-distance transport and protection against UV degradation, MPs alter the spatial and temporal dynamics of viral outbreaks. This environmental stability ensures that pathogens, which would otherwise lose infectivity in open water, remain viable as they transition from degraded aquatic habitats into the human food chain and urban water cycles, thereby linking ecosystemic health to clinical viral pathogenicity.

Because virus adsorption onto micro- and nanoplastics is strongly influenced by particle surface chemistry, this interaction should not be considered uniform across polymer types. As summarized in Figure 1, polymer composition and associated surface features may determine the dominant physicochemical forces involved in virus binding. Polystyrene (PS), due to its aromatic and hydrophobic structure, may favor hydrophobic interactions, π–π interactions, and van der Waals forces with viral capsid or envelope components (8, 11, 80, 82). Polyethylene (PE) and polypropylene (PP), which are predominantly hydrophobic and nonpolar polymers, may interact mainly through hydrophobic and van der Waals forces, although these interactions can be modified by particle size, surface roughness, environmental aging, and the surrounding medium (10, 80, 83). Polyethylene terephthalate (PET), which contains aromatic ester groups and more polar functional groups, may provide additional opportunities for hydrogen bonding as well as hydrophobic and π–π interactions, particularly after environmental weathering introduces oxygen-containing groups on the particle surface (9, 10, 80, 82). In contrast, polyvinyl chloride (PVC), characterized by chlorinated and more polarizable surfaces, may support polar/electrostatic interactions and van der Waals forces, depending on surface charge, additives, aging state, and corona composition (80–83, 91).

The formation of an adsorbed chemical or biomolecular corona further increases this complexity. In environmental or biological media, proteins, lipids, polysaccharides, organic matter, humic substances, pollutants, metal ions, and extracellular nucleic acids can adsorb onto MP/NP surfaces, modifying surface hydrophobicity, charge distribution, colloidal stability, and biological identity (4, 10, 79–82). Therefore, the virus-binding behavior of MP/NPs is likely to depend not only on the pristine polymer structure, but also on the dynamic composition of the adsorbed corona and the environmental or biological matrix in which the interaction occurs (11, 79, 82–84). These polymer-specific mechanisms remain primarily supported by experimental and mechanistic evidence and should not be interpreted as definitive proof of increased viral transmission or disease severity in humans (18, 20, 83, 84).

Synergy between microplastics and viruses: amplification of inflammatory cascades

Beyond serving as environmental vectors, MPs can modulate host responses to viral infections, thereby exacerbating virus-induced inflammation. The convergence of the previously described immunotoxic mechanisms with viral infection pathways creates a synergistic scenario in which MPs function as potent amplifiers of immunopathology. This proposed mechanistic interplay between environmental vectoring, barrier disruption, cellular immune dysfunction, and clinical impact is summarized in Figure 2.

An increasing number of in vitro and in vivo experimental studies have begun to elucidate how MPs/NPs influence the susceptibility, severity, and dynamics of viral infections across diverse biological models—ranging from human cell lines to fish, shrimp, pollinators, and mammals (Table 1). Although these plastic polymers have been traditionally categorized as inert physical contaminants, their direct interaction with viral entities and their capacity to recalibrate the host immune response identify them as emerging biophysical cofactors of significant biomedical and ecotoxicological relevance.

Table 1. Effects of microplastics and nanoplastics on viral infection and host responses in experimental models.

Cell-based studies

Cell-based studies have shown that MPs may facilitate the entry and replication of several human viruses. In human lung epithelial A549 cells, PS-MPs enhanced influenza A virus infection by inhibiting the RIG-I/IRF3 signaling pathway and reducing the expression of IFN-β and antiviral proteins such as IFITM3 (Interferon-induced transmembrane protein 3) (87). Similarly, MPs were found to increase SARS-CoV-2 infectivity in vitro and to induce the expression of inflammatory genes, including TNF-α, IL-8, and caspase-3, further supporting their role as pro-infectious modulators (18).

A novel finding has been reported for vaccinia virus (VACV): in cell cultures, PS-NPs accelerated migrasome formation, a vesicular process involved in viral dissemination, thereby promoting early viral entry into cells and enhancing intracellular spread (88). This represents a novel mechanism of viral pathogenesis mediated by microplastics, which, to date, has not been reported for other environmental contaminants.

Aquatic models

In aquatic models, multiple studies have shown that exposure to MPs and NPs reduces immunity and increases viral replication. In spotted sea bass (Lateolabrax maculatus), chronic exposure to polypropylene microplastics (PP-MPs) induced immunosuppression in lymphoid tissues, thereby promoting the replication of an ulcerative virus (15). Similarly, in juvenile European sea bass, exposure to functionalized PS-NPs reduced the expression of inflammatory and antiviral genes, thereby facilitating infection by nervous necrosis virus (NNV) in both brain cells and live fish (92). Another study in Epinephelus coioides showed that PS-NPs increased the replication of two pathogenic viruses (SGIV and RGNNV) in the spleen and brain, while decreasing the expression of key innate immune genes, including TLRs and interferons (93).

In aquaculture, polyvinyl chloride microplastics (PVC-MPs) were found to enhance both the replication and virulence of white spot syndrome virus (WSSV) in shrimp by suppressing the STING-mediated antiviral response. This effect was associated with lipid metabolic alterations, particularly in phosphatidylcholine, and was partially reversible after the removal of MPs from the environment (89).

Pollinating insects

In bees, oral exposure to PS-MPs caused histological damage to the midgut and increased susceptibility to Israeli acute paralysis virus (IAPV). In addition, transcriptomic analysis revealed alterations in genes associated with lipid metabolism, detoxification, and immune functions (94).

Murine models

Studies in rodents have confirmed that MPs alter the inflammatory response during viral infection. In mice infected with chikungunya virus, MPs consumption prolonged post-infectious joint inflammation and led to increased levels of inflammatory cells, including Th1, NK, and neutrophils (95). In a murine model of mild Coronavirus disease 2019 (COVID-19), co-exposure to inhaled MPs and SARS-CoV-2 did not alter viral load or cause evident histopathological lesions. However, it suppressed the early innate immune response (2 days post-infection) and induced a late peak of pro-inflammatory cytokines (6 days post-infection), a profile consistent with cytokine storm (20).

Ecotoxicology

In freshwater fish (Poecilia reticulata), co-exposure to MPs and SARS-CoV-2 induced behavioral, hepatorenal, and neurochemical alterations, although no clear synergistic effects were identified. Viral infection alone had a greater impact; however, the presence of MPs exacerbated overall environmental toxicity (96). Likewise, in salmon, co-exposure to MPs and infectious hematopoietic necrosis virus was associated with increased mortality, which correlated with higher viral load and greater branchial inflammation, suggesting that MPs compromise physical barriers and increase susceptibility to infection (97).

Conclusions and perspectives: microplastics, inflammation, and viral vulnerability

The interaction between MPs and viruses extends far beyond passive environmental adsorption or transient cytokine modulation. Together, these processes establish a novel inflammatory and virotoxic axis, in which MPs function simultaneously as immunological stressors and pathogenic cofactors. This axis is underpinned by MPs’ ability to induce a persistent basal inflammatory state that disrupts homeostatic equilibrium and primes the host for suboptimal responses to viral challenges. From an integrative perspective, chronic MP exposure induces “inflammatory preconditioning” of tissues, characterized by oxidative stress, constitutive activation of pro-inflammatory pathways (e.g., NF-κB, NLRP3), and compromised epithelial integrity. In this context, MP-induced damage does not necessarily depend on increased viral replication but rather on the amplification of immunopathology and the exacerbation of collateral tissue dysfunction derived from the host’s own antiviral response.

Consequently, MPs should be recognized as universal inflammatory cofactors that can potentiate the severity and duration of viral infections through conserved mechanisms across diverse biological taxa. This phenomenon is particularly critical in respiratory pathologies—such as COVID-19 or influenza—where mucosal barrier integrity and innate immune fitness are primary determinants of clinical prognosis. Inhalation or systemic translocation of MPs may drive profound immunological dysregulation, transforming localized antiviral defenses into uncontrolled systemic inflammation, reminiscent of the cytokine release syndrome observed in severe viral syndromes.

Furthermore, the potential impact of this synergy may extend to the context of chronic viral infections. We hypothesize that persistent exposure to MP/NPs could contribute to the maintenance of low-grade inflammation and immune dysregulation, processes that are also recognized hallmarks of chronic infections such as HIV. Through mechanisms involving oxidative stress, inflammasome activation, and altered immune homeostasis, MP/NPs may exacerbate chronic immune activation, immunosenescence, and functional exhaustion of immune cell populations. However, it is important to emphasize that direct experimental or epidemiological evidence linking MP/NP exposure to HIV progression is currently lacking. Therefore, the proposed relationship remains speculative and should be considered a priority area for future mechanistic and translational research aimed at determining whether environmental plastic exposure contributes to the long-term immunopathology of chronic viral infections.

From a global public health perspective, the convergence of plastic pollution and infectious disease redefines the boundaries of environmental toxicology. MPs are active ecotoxicological agents with potent immunomodulatory capacity, often exacerbated by the co-adsorption of heavy metals and persistent organic pollutants, configuring novel pathogenic synergies in highly contaminated urban and coastal regions. This concern is further supported by evidence showing that plastic-associated chemical contaminants, such as bisphenol A, can exert systemic toxicological effects, including oxidative stress, endocrine disruption, and cellular dysfunction, reinforcing the need to evaluate MP/NPs not only as particles but also as carriers or co-exposure platforms for biologically active plastic-derived chemicals (98).

A key translational implication of these findings is the identification of therapeutic strategies to mitigate MP/NP-induced immune dysfunction. Given the central role of oxidative stress and NLRP3 inflammasome activation in mediating inflammatory responses to MP/NP exposure, pharmacological approaches targeting these pathways may offer protective benefits (56, 99). Experimental studies in other inflammatory conditions have demonstrated that NLRP3 inhibitors can attenuate inflammasome activation and downstream cytokine production (100). Likewise, interventions designed to preserve epithelial barrier integrity and restore immune homeostasis may reduce the systemic consequences of chronic MP/NP exposure (101–103). However, it is important to emphasize that these strategies have not been specifically validated for MP/NP-associated immunotoxicity in humans. Future studies should evaluate whether targeting the NLRP3 inflammasome or the epithelial barrier dysfunction can mitigate the inflammatory and virological consequences associated with environmental plastic exposure.

Despite growing evidence linking MP/NP exposure to immune dysfunction and altered viral responses, the current knowledge is largely derived from in vitro and experimental animal models, warranting caution when extrapolating these findings to human health and clinical practice. Many experimental studies are based on homogeneous particles, controlled polymer compositions, and exposure concentrations that may not accurately reflect the heterogeneous and chronic nature of environmental human exposure (104). Moreover, the translational relevance of these findings is challenged by interspecies differences in immune and physiological responses and by the complexity of real-world exposures, which are shaped by heterogeneous MP/NP characteristics, coexisting environmental contaminants, and host-specific susceptibility factors. Although MPs have been detected in multiple human tissues and biological fluids, including blood, placenta, lungs, and the central nervous system, current evidence primarily demonstrates exposure rather than causality. To date, no robust epidemiological or clinical studies have established a direct association between MP/NP burden and the risk, progression, or severity of viral infections, and the absence of standardized exposure biomarkers and longitudinal human cohorts further limits the assessment of dose-response relationships and long-term health consequences. Consequently, experimental models should primarily be viewed as hypothesis-generating platforms, and future advances in this field will require integrated biomonitoring strategies, prospective epidemiological studies, translational research using environmentally relevant exposure conditions, and quantitative risk assessment frameworks capable of integrating exposure burden, bioavailability, and immune outcomes to define the clinical implications of MP/NP-induced immune dysregulation and viral infection susceptibility.

Addressing this synergistic threat requires a radical transition toward a One Health framework. Determining the magnitude of this crisis will necessitate integrative experimental models using environmentally relevant concentrations, bioavailability assessments, and multi-omic profiling of the MP–immunity–virus axis. Future research must transcend isolated toxicological assessments to investigate how the degradation of the global ‘hydro-cycle’ dictates host-pathogen outcomes. Ultimately, mitigating the impact of MPs on human virological health is inextricably linked to the restoration of the integrity of aquatic and terrestrial ecosystems. Public health strategies must, therefore, prioritize environmental remediation as a primary defense against the emerging threat of plastic-mediated zoonotic and infectious diseases.

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Footnotes

Edited by: Julio Javier diez Casero, University of Valladolid, Spain

Reviewed by: Aditya Gupta, Agricultural Research Service (USDA), United States

Rajkumar Maiti, Bankura Christian College, India