OR.73. Mycobacterium Tuberculosis Derived Toll-like Receptor 2 Ligand Modulate the Function of CD4+ T Cells Directly

2008 ◽  
Vol 127 ◽  
pp. S31
Author(s):  
Xinchun Chen ◽  
Boping Zhou ◽  
Mingxia Zhang
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cd4 T Cells ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2

scholarly journals Toll-Like Receptor 2-Dependent Extracellular Signal-Regulated Kinase Signaling in Mycobacterium tuberculosis-Infected Macrophages Drives Anti-Inflammatory Responses and Inhibits Th1 Polarization of Responding T Cells

2015 ◽  
Vol 83 (6) ◽  
pp. 2242-2254 ◽  
Author(s):  
Edward T. Richardson ◽  
Supriya Shukla ◽  
David R. Sweet ◽  
Pamela A. Wearsch ◽  
Philip N. Tsichlis ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Erk Signaling ◽  
Toll Like Receptor ◽  
Content Type ◽  
Extracellular Signal ◽  
Toll Like Receptor 2 ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Th1 Polarization

Mycobacterium tuberculosissurvives within macrophages and employs immune evasion mechanisms to persist in the host. Protective T helper type 1 (Th1) responses are induced, and the immune response in most individuals is sufficient to restrictM. tuberculosisto latent infection, but most infections are not completely resolved. As T cells and macrophages respond, a balance is established between protective Th1-associated and other proinflammatory cytokines, such as interleukin-12 (IL-12), interferon gamma (IFN-γ), and tumor necrosis factor alpha, and anti-inflammatory cytokines, such as IL-10. The mechanisms by whichM. tuberculosismodulates host responses to promote its survival remain unclear. In these studies, we demonstrate thatM. tuberculosisinduction of IL-10, suppression of IL-12, and inhibition of class II major histocompatibility complex (MHC-II) molecules in infected macrophages are all driven by Toll-like receptor 2 (TLR2)-dependent activation of the extracellular signal-regulated kinases (ERK). Elimination of ERK signaling downstream of TLR2 by pharmacologic inhibition with U0126 or genetic deletion ofTpl2blocks IL-10 secretion and enhances IL-12 p70 secretion. We demonstrate thatM. tuberculosisregulation of these pathways in macrophages affects T cell responses to infected macrophages. Thus, genetic blockade of the ERK pathway inTpl2−/−macrophages enhances Th1 polarization and IFN-γ production by antigen-specific CD4+T cells responding toM. tuberculosisinfection. These data indicate thatM. tuberculosisand its potent TLR2 ligands activate ERK signaling in macrophages to promote anti-inflammatory macrophage responses and blunt Th1 responses against the pathogen.

scholarly journals Engagement of Toll‐Like Receptor 2 on CD4+T Cells Facilitates Local Immune Responses in Patients with Tuberculous Pleurisy

2009 ◽  
Vol 200 (3) ◽  
pp. 399-408 ◽  
Author(s):  
Xinchun Chen ◽  
Mingxia Zhang ◽  
Xiuyun Zhu ◽  
Qunyi Deng ◽  
Haiying Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2 ◽  
Tuberculous Pleurisy

scholarly journals The Mycobacterium tuberculosis 19-Kilodalton Lipoprotein Inhibits Gamma Interferon-Regulated HLA-DR and FcγR1 on Human Macrophages through Toll-Like Receptor 2

2003 ◽  
Vol 71 (8) ◽  
pp. 4487-4497 ◽  
Author(s):  
Adam J. Gehring ◽  
Roxana E. Rojas ◽  
David H. Canaday ◽  
David L. Lakey ◽  
Clifford V. Harding ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Gamma Interferon ◽  
Toll Like Receptor ◽  
Human Macrophages ◽  
Mhc Ii ◽  
Cell Immunity ◽  
Hla Dr ◽  
Toll Like Receptor 2 ◽  
Ifn Γ

ABSTRACT Mycobacterium tuberculosis survives in macrophages in the face of acquired CD4+ T-cell immunity, which controls but does not eliminate the organism. Gamma interferon (IFN-γ) has a central role in host defenses against M. tuberculosis by activating macrophages and regulating major histocompatibility complex class II (MHC-II) antigen (Ag) processing. M. tuberculosis interferes with IFN-γ receptor (IFN-γR) signaling in macrophages, but the molecules responsible for this inhibition are poorly defined. This study determined that the 19-kDa lipoprotein from M. tuberculosis inhibits IFN-γ-regulated HLA-DR protein and mRNA expression in human macrophages. Inhibition of HLA-DR expression was associated with decreased processing and presentation of soluble protein Ags and M. tuberculosis bacilli to MHC-II-restricted T cells. Inhibition of HLA-DR required prolonged exposure to 19-kDa lipoprotein and was blocked with a monoclonal antibody specific for Toll-like receptor 2 (TLR-2). The 19-kDa lipoprotein also inhibited IFN-γ-induced expression of FcγRI. Thus, M. tuberculosis, through 19-kDa lipoprotein activation of TLR-2, inhibits IFN-γR signaling in human macrophages, resulting in decreased MHC-II Ag processing and recognition by MHC-II-restricted CD4 T cells. These findings provide a mechanism for M. tuberculosis persistence in macrophages.

scholarly journals Toll like Receptor 2 engagement on CD4+T cells promotes TH9 differentiation and function

2017 ◽  
Vol 47 (9) ◽  
pp. 1513-1524 ◽  
Author(s):  
Ahmad Faisal Karim ◽  
Scott M. Reba ◽  
Qing Li ◽  
W. Henry Boom ◽  
Roxana E. Rojas
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2 ◽  
And Function

scholarly journals Cutting Edge: Control of Mycobacterium tuberculosis Infection by a Subset of Lung Parenchyma–Homing CD4 T Cells

2014 ◽  
Vol 192 (7) ◽  
pp. 2965-2969 ◽  
Author(s):  
Shunsuke Sakai ◽  
Keith D. Kauffman ◽  
Jason M. Schenkel ◽  
Cortez C. McBerry ◽  
Katrin D. Mayer-Barber ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cd4 T Cells ◽  
Lung Parenchyma ◽  
Cutting Edge ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection
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