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Ludovica F Butto

Ludovica F Butto

Technische Universität Munchen Weihenstephan, Germany

Title: TLR2 located in macrophage sub cellular compartments negatively regulates TLR4 mediated inflammatory response to internalized bacteria

Biography

Biography: Ludovica F Butto

Abstract

Recognition of microbes by toll-like receptors (TLRs) is critical for initiation of appropriate innate and adaptive immune responses. How crosstalk between TLRs situated in various cellular locations contributes to host-microbe dialogue and immunoregulation is presently unclear. Here we report a dual role for TLR2 in regulating the response of macrophages to internalized bacteria. Cell surface TLR2 initiated an inflammatory response while sub cellular TLR2 negatively regulated a TLR4-mediated hyper-inflammatory response that was phagocytosis dependent and driven by a type-I interferon autocrine loop. TLR2 deficient macrophages were hyper responsive to commensal and pathogenic bacteria and developed an M1 like phenotype, which was absent in TLR2/TLR4 deficient macrophages. Our findings identify sub cellular TLR2 as being important for the negative regulation of inappropriate TLR4 mediated inflammatory responses to bacteria.