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

Mycobacterial infection induces a specific human innate immune response.

Author information

1
Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.
2
Committee on Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, Illinois, USA.
3
Mycobacterial Genetics Unit, Institut Pasteur, Paris, France.
4
Department of Genetics, CHU Sainte-Justine Research Center, Montreal, Québec, Canada.
5
Department of Pediatrics, University of Montreal, Montreal, Québec, Canada.

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.

PMID:
26586179
PMCID:
PMC4653619
DOI:
10.1038/srep16882
[Indexed for MEDLINE]
Free PMC Article

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