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Eur J Immunol. 2014 May;44(5):1399-409. doi: 10.1002/eji.201344039. Epub 2014 Feb 13.

MyD88 signalling in myeloid cells is sufficient to prevent chronic mycobacterial infection.

Author information

1
Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hanover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hanover, Germany.

Abstract

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis that is responsible for almost 1.5 million deaths per year. Sensing of mycobacteria by the host's immune system relies on different families of receptors present on innate immune cells. Amongst them, several members of the TLR family are involved in the activation of immune cells by mycobacteria, yet the in vivo contribution of individual TLRs to the protective immune response remains controversial. On the contrary, MyD88, the adaptor molecule for most TLRs, plays a non-redundant role in the protection against tuberculosis and mice with a complete germline deletion of MyD88 succumb very early to infection. MyD88 is expressed in both immune and non-immune cells, but it is not clear whether control of mycobacteria requires ubiquitous or cell-type specific MyD88 expression. Therefore, using novel conditional switch-on mouse models, we aimed to investigate the importance of MyD88 signalling in DCs and macrophages for the induction of protective effector mechanisms against mycobacterial infection. We conclude that specific reactivation of MyD88 signalling in CD11c- or lysozyme M-expressing myeloid cells during Mycobacterium bovis Bacille Calmette-Guerin infection is sufficient to restore systemic and local inflammatory cytokine production and to control pathogen burden.

KEYWORDS:

Conditional switch-on mice; Dendritic cells; Macrophages; MyD88; Mycobacteria

PMID:
24435955
DOI:
10.1002/eji.201344039
[Indexed for MEDLINE]
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