Suppression of Toll-like receptor 2–mediated proinflammatory responses by Mycobacterium tuberculosis protein Rv3529c

Autor: Attinder Chadha, Priya Gupta, Brijendra K Tiwari, Krishnamurthy Natarajan, Upasana Bandyopadhyay, K K Bhattacharyya, Yogendra Singh, Vani Brahamachari, Pawan Malhotra, Sonam Popli, Rajagopal Raman
Rok vydání: 2017
Předmět:
Zdroj: Journal of Leukocyte Biology. 102:1249-1259
ISSN: 1938-3673
0741-5400
DOI: 10.1189/jlb.4a0217-042r
Popis: Microorganisms are known to devise various strategies to thwart protective responses by the host. One such strategy is to incorporate sequences and domains in their genes/proteins that have similarity to various domains of the host proteins. In this study, we report that Mycobacterium tuberculosis protein Rv3529c exhibits significant similarity to the death domain of the TLR pathway adaptor protein MyD88. Incubation of macrophages with Rv3529c specifically inhibited TLR2-mediated proinflammatory responses. This included attenuated oxidative burst, reduced phosphorylation of MAPK-ERK, reduced activation of transcription factor NF-κB and reduced secretion of proinflammatory cytokines IFN-γ, IL-6, and IL-17A with a concomitant increased secretion of suppressor cytokines IL-10 and TGF-β. Importantly, Rv3529c significantly inhibited TLR2-induced association of MyD88 with IRAK1 by competitively binding with IRAK1. Further, Rv3529c mediated inhibition of apoptosis and phagosome–lysosome fusion. Lastly, incubation of macrophages with Rv3529c increased bacterial burden inside macrophages. The data presented show another strategy evolved by M. tuberculosis toward immune evasion that centers on incorporating sequences in proteins that are similar to crucial proteins in the innate immune system of the host.
Databáze: OpenAIRE
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