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Mycobacterium tuberculosis impairs dendritic cell response by altering CD1b, DC‐SIGN and MR profile
Author(s) -
Balboa Luciana,
Romero María Mercedes,
Yokobori Noemí,
Schierloh Pablo,
Geffner Laura,
Basile Juan I,
Musella Rosa M,
Abbate Eduardo,
Barrera Silvia,
Sasiain María C,
Alemán Mercedes
Publication year - 2010
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2010.22
Subject(s) - cd86 , mycobacterium tuberculosis , tuberculosis , dendritic cell , population , immune system , immunology , monocyte , biology , cd80 , t cell , microbiology and biotechnology , cytotoxic t cell , medicine , cd40 , in vitro , pathology , genetics , environmental health
During a chronic infection such as tuberculosis, the pool of tissue dendritic cells (DC) must be renewed by recruitment of both circulating DC progenitors and monocytes (Mo). However, the microenvironment of the inflammatory site affects Mo differentiation. As DC are critical for initiating a Mycobacterium tuberculosis ‐specific T‐cell response, we argue that interference of M. tuberculosis with a correct DC generation would signify a mechanism of immune evasion. In this study, we showed that early interaction of γ‐irradiated M. tuberculosis with Mo subverts DC differentiation in vitro . We found that irradiated M. tuberculosis effect involves (1) the loss of a significant fraction of monocyte population and (2) an altered differentiation process of the surviving monocyte subpopulation. Moreover, in the absence of irradiated M. tuberculosis, DC consist in a major DC‐specific intercellular adhesion molecule 3‐grabbing non‐integrin receptor (DC‐SIGN high )/CD86 low and minor DC‐SIGN low /CD86 high subpopulations, whereas in the presence of bacteria, there is an enrichment of DC‐SIGN low /CD86 high population. Besides, this population enlarged by irradiated M. tuberculosis, which is characterized by a reduced CD1b expression, correlates with a reduced induction of specific T‐lymphocyte proliferation. The loss of CD1molecules partially involves toll‐like receptors (TLR‐2)/p38 MAPK activation. Finally, several features of Mo, which have been differentiated into DC in the presence of irradiated M. tuberculosis , resemble the features of DC obtained from patients with active tuberculosis. In conclusion, we suggest that M. tuberculosis escapes from acquired immune response in tuberculosis may be caused by an altered differentiation into DC leading to a poor M. tuberculosis ‐specific T‐cell response.