{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T20:58:27Z","timestamp":1770238707929,"version":"3.49.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2009,11,1]],"date-time":"2009-11-01T00:00:00Z","timestamp":1257033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u223c15 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.<\/jats:p>","DOI":"10.4049\/jimmunol.0901367","type":"journal-article","created":{"date-parts":[[2009,10,31]],"date-time":"2009-10-31T00:45:43Z","timestamp":1256949943000},"page":"6269-6281","source":"Crossref","is-referenced-by-count":181,"title":["The PPE18 of <i>Mycobacterium tuberculosis<\/i> Interacts with TLR2 and Activates IL-10 Induction in Macrophage"],"prefix":"10.1093","volume":"183","author":[{"given":"Shiny","family":"Nair","sequence":"first","affiliation":[{"name":"Centre for DNA Fingerprinting and Diagnostics (CDFD) , Nampally, Hyderabad,","place":["India"]}]},{"given":"Poongothai A","family":"Ramaswamy","sequence":"additional","affiliation":[{"name":"Centre for DNA Fingerprinting and Diagnostics (CDFD) , Nampally, Hyderabad,","place":["India"]}]},{"given":"Sudip","family":"Ghosh","sequence":"additional","affiliation":[{"name":"National Institute of Nutrition (ICMR) , Jamai-Osmania PO, Hyderabad,","place":["India"]}]},{"given":"Dhananjay C","family":"Joshi","sequence":"additional","affiliation":[{"name":"Centre for DNA Fingerprinting and Diagnostics (CDFD) , Nampally, Hyderabad,","place":["India"]}]},{"given":"Niteen","family":"Pathak","sequence":"additional","affiliation":[{"name":"Centre for DNA Fingerprinting and Diagnostics (CDFD) , Nampally, Hyderabad,","place":["India"]}]},{"given":"Imran","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB) , New Delhi,","place":["India"]}]},{"given":"Pawan","family":"Sharma","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB) , New Delhi,","place":["India"]}]},{"given":"Seyed E","family":"Hasnain","sequence":"additional","affiliation":[{"name":"Centre for DNA Fingerprinting and Diagnostics (CDFD) , Nampally, Hyderabad,","place":["India"]},{"name":"Jawaharlal Nehru Centre for Advanced Scientific Research , Bangalore,","place":["India"]},{"name":"University of Hyderabad , P.O. Central University, Hyderabad,","place":["India"]},{"name":"Institute of Life Sciences, Hyderabad Central University Campus , Hyderabad,","place":["India"]}]},{"given":"Shekhar C","family":"Mande","sequence":"additional","affiliation":[{"name":"Centre for DNA Fingerprinting and Diagnostics (CDFD) , Nampally, Hyderabad,","place":["India"]}]},{"given":"Sangita","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Centre for DNA Fingerprinting and Diagnostics (CDFD) , Nampally, Hyderabad,","place":["India"]}]}],"member":"286","published-online":{"date-parts":[[2009,11,15]]},"reference":[{"key":"2025032709514218400_R1","first-page":"537","article-title":"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.","volume-title":"Nature","year":"1998"},{"key":"2025032709514218400_R2","first-page":"95","article-title":"Evolution and expansion of the Mycobacterium tuberculosis PE and PPE multigene families and their association with the duplication of the ESAT-6 (esx) gene cluster regions.","volume-title":"BMC Evol. 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