Host Genetics and Microbial Determinants of Infectious Disease Severity

Infectious diseases continue to pose a major global health burden, yet individuals exposed to the same pathogen frequently exhibit markedly different clinical outcomes, ranging from asymptomatic infection to severe or fatal disease. This variability reflects a complex interplay between host genetic factors and microbial determinants of pathogenicity. Host genetic variability plays a central role in shaping susceptibility and disease severity. Polymorphisms in genes involved in innate and adaptive immunity, such as pattern recognition receptors, interferon signalling pathways, cytokines, and antigen presentation molecules, can influence pathogen recognition, immune activation, and inflammatory responses. Increasing evidence from genome-wide association studies and functional analyses demonstrates that host genetic architecture significantly contributes to disease outcomes across a broad spectrum of infections, including COVID-19, tuberculosis, and viral haemorrhagic fevers. This Research Topic aims to elucidate the complex genetic and molecular interplay that drives variability in infectious disease outcomes. By combining host genomics, microbial evolution, and immunopathology, the objective is to uncover the mechanisms by which host and pathogen genetic factors jointly shape infection severity. Key questions include: How do host polymorphisms in immune regulatory genes affect pathogen recognition and response? What microbial genomic features are linked to virulence and immune evasion? Can integrative models encompassing both genomic landscapes improve strategies for diagnosis, risk stratification, and therapy? This topic also seeks to highlight technological advances, such as multi-omics integration and high-throughput screening, that enable deeper exploration of these interactions. To gather further insights into the genetic and molecular factors influencing infectious disease severity, we welcome submissions that span different host–pathogen systems and analytical approaches. We encourage contributions addressing, but not limited to, the following themes: • Host genetic variation in innate and adaptive immune responses • Microbial genomics and evolution of virulence factors • Host–pathogen co-evolution and immune evasion mechanisms • Functional genomics and systems biology approaches to infection outcomes • Multi-omics integration to link host and microbial determinants • Translational applications for personalized therapeutics, diagnostics, and vaccines • Host–microbiome interactions and their implications for infection severity We welcome original research, reviews, mini-reviews, and perspectives that advance our understanding of host–pathogen genetic interactions and their translational potential. Topic editors: Svetlana Khaiboullina, Manoj Baranwal, Nayeli Alva-Murillo, Samira Tarashi, Gulcin Tezcan Durmus Source: https://www.frontiersin.org/research-topics/81323/host-genetics-and-microbial-determinants-of-infectious-disease-severity