ABSTRACT
ABSTRACT Host genes, together with microbial and environmental factors, determine susceptibility, severity, and course of respiratory tract infections. Seldom occurring mutations in a single gene may cause a dramatically enhanced severity of infection. However, usually the course of infection is influenced by several, frequently occurring gene variants that each has a small positive or negative effect. The variation in disease susceptibility or severity accounted for by genetic factors may vary considerably for specific infections, but appears quite high for tuberculosis. Genetic studies emphasize that interferon-γactivated macrophage function is critical in controlling mycobacterial infection. Genes affecting respiratory syncytial virus (RSV) infections especially influence the innate immune system and the Th2 cytokine pathway. Genetic factors influencing pneumococcal infections relate to the complement pathway, opsonization, and phagocytosis. Knowledge of host genetic variants adds to our understanding of pathogenesis, and may identify critical steps to which prevention and therapy may be directed. New treatments and vaccines may be tailored to host genetic profile, for example to ethnic group or individual, or not. Genetic studies may further identify individuals that respond poorly to vaccination, or that develop adverse events upon vaccination or infection. Future work will expand our knowledge of gene variants that affect either a single or several respiratory tract infectious and allergic disorders.
