Mycobacterial Infection Induces a Specific Human Innate Immune Response

Sci Rep. 2015 Nov 20;5:16882. doi: 10.1038/srep16882.

Abstract

The innate immune system provides the first response to infection and is now recognized to be partially pathogen-specific. Mycobacterium tuberculosis (MTB) is able to subvert the innate immune response and survive inside macrophages. Curiously, only 5-10% of otherwise healthy individuals infected with MTB develop active tuberculosis (TB). We do not yet understand the genetic basis underlying this individual-specific susceptibility. Moreover, we still do not know which properties of the innate immune response are specific to MTB infection. To identify immune responses that are specific to MTB, we infected macrophages with eight different bacteria, including different MTB strains and related mycobacteria, and studied their transcriptional response. We identified a novel subset of genes whose regulation was affected specifically by infection with mycobacteria. This subset includes genes involved in phagosome maturation, superoxide production, response to vitamin D, macrophage chemotaxis, and sialic acid synthesis. We suggest that genetic variants that affect the function or regulation of these genes should be considered candidate loci for explaining TB susceptibility.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bayes Theorem
  • Cells, Cultured
  • Gene Expression / immunology*
  • Gene Expression Profiling / methods
  • Gene Ontology
  • Genetic Predisposition to Disease / genetics
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology*
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Mycobacterium bovis / immunology
  • Mycobacterium bovis / physiology
  • Mycobacterium smegmatis / immunology
  • Mycobacterium smegmatis / physiology
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / physiology
  • Principal Component Analysis
  • Quantitative Trait Loci / genetics
  • Quantitative Trait Loci / immunology
  • Salmonella typhimurium / immunology
  • Salmonella typhimurium / physiology
  • Species Specificity
  • Staphylococcus epidermidis / immunology
  • Staphylococcus epidermidis / physiology
  • Tuberculosis / genetics
  • Tuberculosis / immunology
  • Tuberculosis / microbiology
  • Yersinia pseudotuberculosis / immunology
  • Yersinia pseudotuberculosis / physiology