title: TLR2 deficiency by compromising p19 (IL-23) expression limits Th 17 cell responses to Mycobacterium tuberculosis.
abstract: CD4(+) T(h)1 cells producing IFN-γ are of extreme importance in controlling infections by Mycobacterium tuberculosis both in mice and in men. In addition to IFN-γ-producing T cells, IL-17-producing T cells (T(h)17) have been observed during mycobacterial infections. Nevertheless, their contribution for the host immune response to mycobacteria as well as the signals triggering M. tuberculosis -specific T(h)17 cell differentiation and maintenance are not fully understood. We show that signaling via Toll-like receptor (TLR) 2 has a major impact on the regulation of p19 (IL-23) expression in response to M. tuberculosis and therefore on the establishment of T(h)17 cell responses to M. tuberculosis infection. Diminished T(h)17 responses in the lung of M. tuberculosis -infected TLR2-deficient animals were not caused by defective cell differentiation in the draining lymph node (LN) but rather by reduced maintenance at the site of infection. Consistent with the decreased numbers of T(h)17 cells in the lungs of infected TLR2-deficient animals, we observed reduced expression of CXCL9, CXCL10 and CXCL11, chemokines involved in recall responses to M. tuberculosis. Our data provides insights into the TLR2 role in infection with M. tuberculosis, with implications in pathophysiology of the disease and vaccine design.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
authors.forename: Maria
authors.initials: M
authors.lastname: Teixeira-Coelho
authors.forename: Andrea
authors.initials: A
authors.lastname: Cruz
authors.forename: Jenny
authors.initials: J
authors.lastname: Carmona
authors.forename: Carole
authors.initials: C
authors.lastname: Sousa
authors.forename: Daniela
authors.initials: D
authors.lastname: Ramos-Pereira
authors.forename: Ana Laura
authors.initials: AL
authors.lastname: Saraiva
authors.forename: Marc
authors.initials: M
authors.lastname: Veldhoen
authors.forename: Jorge
authors.initials: J
authors.lastname: Pedrosa
authors.forename: António G
authors.initials: AG
authors.lastname: Castro
authors.forename: Margarida
authors.initials: M
authors.lastname: Saraiva
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D020381:Interleukin-17 / Q000276:immunology; D053760:Interleukin-23 Subunit p19 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009164:Mycobacterium Infections / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000172:deficiency* / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D051195:Toll-Like Receptor 2