Human genetic susceptibility to intracellular pathogens

• Published in: Immunological reviews Vol. 240; no. 1; pp. 105 - 116
• Main Authors: Vannberg, Fredrik O, Chapman, Stephen J, Hill, Adrian V.S
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2011; Blackwell
• Subjects: AIDS; Analytical, structural and metabolic biochemistry; bacterial; Biological and medical sciences; Communicable Diseases - genetics; Communicable Diseases - immunology; Communicable Diseases - physiopathology; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Hepatitis - genetics; HIV Infections - genetics; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Leprosy - genetics; Malaria - genetics; Medical sciences; Mycobacterium; Tuberculosis - genetics; viral; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virus Diseases - genetics; Human; Immunopathology; infectious diseases; AIDS; Biochemistry; Immune deficiency; Infection; Virus; Sensitivity; bacterial; Viral disease; Pathogenic; Bacteriosis; Bacteria; Genetics; viral; Intracellular
• ISSN: 0105-2896; 1600-065X; 1600-065X
• DOI: 10.1111/j.1600-065X.2010.00996.x

Intracellular pathogens contribute to a significant proportion of infectious disease morbidity and mortality worldwide. Increasing evidence points to a major role for host genetics in explaining inter-individual variation in susceptibility to infectious diseases. A number of monogenic disorders predisposing to infectious disease have been reported, including susceptibility to intracellular pathogens in association with mutations in genes of the interleukin-12/interleukin-23/interferon-γ axis. Common genetic variants have also been demonstrated to regulate susceptibility to intracellular infection, for example the CCR5Δ32 polymorphism that modulates human immunodeficiency virus-1 (HIV-1) disease progression. Genome-wide association study approaches are being increasingly utilized to define genetic variants underlying susceptibility to major infectious diseases. This review focuses on the current state-of-the-art in genetics and genomics as pertains to understanding the genetic contribution to human susceptibility to infectious diseases caused by intracellular pathogens such as tuberculosis, leprosy, HIV-1, hepatitis, and malaria, with a particular emphasis on insights from recent genome-wide approaches. The results from these studies implicate common genetic variants in novel molecular pathways involved in human immunity to specific pathogens.