Microbial Amyloids Induce Interleukin 17A (IL-17A) and IL-22 Responses via Toll-Like Receptor 2 Activation in the Intestinal Mucosa
Autor: | Steven G. Biesecker, Çagla Tükel, Jessalyn H. Nishimori, Jui-Hung Yen, R. Paul Wilson, Gertrude O. Oppong, Doina Ganea, Maria G. Winter, Brian P. Butler, Renée M. Tsolis, Glenn J. Rapsinski, Tiffanny N. Newman |
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Rok vydání: | 2012 |
Předmět: |
Salmonella typhimurium
Amyloid Immunology Biology Microbiology Interleukin 22 Mice Intestinal mucosa Animals Humans Cytotoxic T cell Intestinal Mucosa Cells Cultured Host Response and Inflammation Mice Inbred BALB C Toll-like receptor Interleukins Interleukin-17 Th1 Cells Colitis Toll-Like Receptor 2 Disease Models Animal TLR2 Infectious Diseases Th17 Cells Female Parasitology Interleukin 17 HT29 Cells CD8 |
Zdroj: | Infection and Immunity. 80:4398-4408 |
ISSN: | 1098-5522 0019-9567 |
Popis: | The Toll-like receptor 2 (TLR2)/TLR1 receptor complex responds to amyloid fibrils, a common component of biofilm material produced by members of the phyla Firmicutes , Bacteroidetes , and Proteobacteria . To determine whether this TLR2/TLR1 ligand stimulates inflammatory responses when bacteria enter intestinal tissue, we investigated whether expression of curli amyloid fibrils by the invasive enteric pathogen Salmonella enterica serotype Typhimurium contributes to T helper 1 and T helper 17 responses by measuring cytokine production in the mouse colitis model. A csgBA mutant, deficient in curli production, elicited decreased expression of interleukin 17A (IL-17A) and IL-22 in the cecal mucosa compared to the S . Typhimurium wild type. In TLR2-deficient mice, IL-17A and IL-22 expression was blunted during S . Typhimurium infection, suggesting that activation of the TLR2 signaling pathway contributes to the expression of these cytokines. T cells incubated with supernatants from bone marrow-derived dendritic cells (BMDCs) treated with curli fibrils released IL-17A in a TLR2-dependent manner in vitro . Lower levels of IL-6 and IL-23 production were detected in the supernatants of the TLR2-deficient BMDCs treated with curli fibrils. Consistent with this, three distinct T-cell populations—CD4 + T helper cells, cytotoxic CD8 + T cells, and γδ T cells—produced IL-17A in response to curli fibrils in the intestinal mucosa during S . Typhimurium infection. Notably, decreased IL-6 expression by the dendritic cells and decreased IL-23 expression by the dendritic cells and macrophages were observed in the cecal mucosa of mice infected with the curli mutant. We conclude that TLR2 recognition of bacterial amyloid fibrils in the intestinal mucosa represents a novel mechanism of immunoregulation, which contributes to the generation of inflammatory responses, including production of IL-17A and IL-22, in response to bacterial entry into the intestinal mucosa. |
Databáze: | OpenAIRE |
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