The PPE18 of Mycobacterium tuberculosis interacts with TLR2 and activates IL-10 induction in macrophage

Shiny Nair, Poongothai A. Ramaswamy, Sudip Ghosh, Dhananjay C. Joshi, Niteen Pathak, Imran Siddiqui, Pawan Sharma, Seyed E. Hasnain, Shekhar C. Mande, Sangita Mukhopadhyay

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Abstract

The pathophysiological functions of proline-glutamic acid (PE)/proline-proline-glutamic acid (PPE) family of proteins of Mycobacterium tuberculosis are not well understood. In this study, we demonstrate that one of the PPE proteins, PPE18 can stimulate macrophages to secrete IL-10, known to favor a Th2 type response. The recombinant PPE18 was found to specifically interact with the TLR2 leading to an early and sustained activation of p38 MAPK, which is critical for IL-10 induction. In silico docking analyses and mutation experiments indicate that PPE18 specifically interacts with the leucine rich repeat 11-15 domain of TLR2 and the site of interaction is different from that of a synthetic lipopeptide Pam3CSK4 known to activate predominantly ERK 1/2. When PMA-differentiated THP-1 macrophages were infected with a mutant Mycobacterium tuberculosis strain lacking the PPE18, produced poorer levels of IL-10 as compared with those infected with the wild-type strain. In contrast, an M. smegmatis strain overexpressing the PPE18 induced higher levels of IL-10 in infected macrophages. Our data indicate that the PPE18 protein may trigger an anti-inflammatory response by inducing IL-10 production.

Original languageEnglish
Pages (from-to)6269-6281
Number of pages13
JournalJournal of Immunology
Volume183
Issue number10
DOIs
Publication statusPublished - Nov 15 2009

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ASJC Scopus subject areas

  • Immunology

Cite this

Nair, S., Ramaswamy, P. A., Ghosh, S., Joshi, D. C., Pathak, N., Siddiqui, I., Sharma, P., Hasnain, S. E., Mande, S. C., & Mukhopadhyay, S. (2009). The PPE18 of Mycobacterium tuberculosis interacts with TLR2 and activates IL-10 induction in macrophage. Journal of Immunology, 183(10), 6269-6281. https://doi.org/10.4049/jimmunol.0901367