Role of TLR2-dependent IL-10 production in the inhibition of the initial IFN-γ T cell response to Porphyromonas gingivalis.
P.g., a Gram-negative bacterium, is one of the main etiological agents of the chronic inflammatory disease, periodontitis. Disease progression is thought to occur as a result of an inadequate immune response, which although happens locally, can also occur distally as a result of the dissemination of P.g. into the circulation. As IL-10 and TLR2 are pivotal molecules in the immune response that P.g. elicits, we hypothesized that TLR2-mediated IL-10 production, following the initial systemic exposure to P.g., inhibits the IFN-γ T cell response. To address this hypothesis, mice were primed with P.g., and the types of cells producing IL-10 and the capacity of T cells to produce IFN-γ following blocking or neutralization of IL-10 were assessed. Our results showed that upon initial encounter with P.g., splenic T cells and CD11b(+) cells produce IL-10, which when neutralized, resulted in a substantial increase in IFN-γ production by T cells. Furthermore, IL-10 production was dependent on TLR2/1 signaling, partly in response to the major surface protein, FimA of P.g. In addition, P.g. stimulation resulted in the up-regulation of PD-1 and its ligand PD-L1 on CD4 T cells and CD11b(+) cells, respectively. Up-regulation of PD-1 was partially dependent on IL-10 but independent of TLR2 or FimA. These results highlight the role of IL-10 in inhibiting T cell responses to the initial systemic P.g. exposure and suggest multiple inhibitory mechanisms potentially used by P.g. to evade the host's immune response, thus allowing its persistence in the host.
University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294-2170, USA. meow@uab.edu
Dalia E
DE
Gaddis
Craig L
CL
Maynard
Casey T
CT
Weaver
Suzanne M
SM
Michalek
Jannet
J
Katz
D000818:Animals; D016866:Bacteroidaceae Infections / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016966:Porphyromonas gingivalis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism
C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D016753:Interleukin-10; D007371:Interferon-gamma