Open AccessCLEC9A modulates macrophage-mediated neutrophil recruitment in response to heat-killed Mycobacterium tuberculosis H37Ra
Author(s) -
AnChieh Cheng,
Kuang-Yao Yang,
NienJung Chen,
Tsui-Ling Hsu,
Ruwen Jou,
Shie-Liang Hsieh,
PingHui Tseng
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0186780
Subject(s) - innate immune system , biology , mycobacterium tuberculosis , microbiology and biotechnology , acquired immune system , immune system , pattern recognition receptor , lipoarabinomannan , receptor , immunology , tuberculosis , medicine , biochemistry , pathology
Tuberculosis is a fatal human infectious disease caused by Mycobacterium tuberculosis ( M . tuberculosis ) that is prevalent worldwide. Mycobacteria differ from other bacteria in that they have a cell wall composed of specific surface glycans that are the major determinant of these organisms' pathogenicity. The interaction of M . tuberculosis with pattern recognition receptors (PRRs), in particular C-type lectin receptors (CLRs), on the surface of macrophages plays a central role in initiating innate and adaptive immunity, but the picture as a whole remains a puzzle. Defining novel mechanisms by which host receptors interact with pathogens in order to modulate a specific immune response is an area of intense research. In this study, based on an in vitro lectin binding assay, CLEC9A (DNGR-1) is identified as a novel CLR that binds with mycobacteria. Our results with CLEC9A-knocked down cells and a CLEC9A-Fc fusion protein as blocking agents show that CLEC9A is involved in the activation of SYK and MAPK signaling in response to heat-killed M . tuberculosis H37Ra treatment, and it then promotes the production of CXCL8 and IL-1β in macrophages. The CXCL8 and IL-1β secreted by the activated macrophages are critical to neutrophil recruitment and activation. In a in vivo mouse model, when the interaction between CLEC9A and H37Ra is interfered with by treatment with CLEC9A-Fc fusion protein, this reduces lung inflammation and cell infiltration. These findings demonstrate that CLEC9A is a specialized receptor that modulates the innate immune response when there is a mycobacterial infection.