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Genetic variation of innate immune response genes in invasive pneumococcal and meningococcal disease applied to the pathogenesis of meningitis

Genes & Immunity volume 12, pages 321–334 (2011)Cite this article

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Abstract

The susceptibility, severity and prognosis of infectious diseases depend on the ability of the host immune system to respond to pathogens. Genetic variation of immune response genes is associated with susceptibility to and severity of infectious diseases. Bacterial meningitis (BM) is a serious and life-threatening infectious disease of the central nervous system (CNS). Despite adequate antibiotic treatment and immunization strategies, mortality remains high, especially in developing countries. Streptococcus pneumoniae and Neisseria meningitidis are the two most common causative microorganisms of BM worldwide. The pathogenesis of BM starts with mucosal bacterial colonization, followed by invasion and survival of bacteria in the bloodstream, crossing of the blood–brain barrier, finally causing infection in the CNS, where host defense is less adequate. Host defense to BM starts with a complex cascade of pathogen recognition and subsequent intracellular signaling causing transcription of genes leading to the production of inflammatory mediators. Although this immune reaction is essential for killing microbes, it is also associated with damage to healthy cells and thus adverse disease outcome. This review provides an overview of the pathogenesis of invasive pneumococcal disease and invasive meningococcal disease related to the influence of genetic variation in genes involved in innate immunity, focusing on BM.

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  1. M S Sanders and G T J van Well: These authors contributed equally to this work as shared first authors.

Authors and Affiliations

  1. Department of Pathology, Laboratory for Immunogenetics, VU University Medical Center, Amsterdam, The Netherlands

    M S Sanders, S Ouburg & S A Morré

  2. Department of Pediatric Infectious Diseases, Immunology and Rheumatology, VU University Medical Center, Amsterdam, The Netherlands

    M S Sanders, G T J van Well & A M van Furth

  3. Department of Pediatrics, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands

    G T J van Well

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  1. M S Sanders
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Sanders, M., van Well, G., Ouburg, S. et al. Genetic variation of innate immune response genes in invasive pneumococcal and meningococcal disease applied to the pathogenesis of meningitis. Genes Immun 12, 321–334 (2011). https://doi.org/10.1038/gene.2011.20

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