Journal of Clinical and Cellular Immunology
Open Access

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

Conference Series LLC Joint International Event on 5^th European Immunology & Innate Immunity

July 21-23, 2016 Berlin, Germany

Ludovica F Butto, Silvia Melgar, John OCallaghan, Ian B Jeffery, Hugh M B Harris, John MacSharry, Fergus Shanahan, Paul W OToole and Ken Nally

Technische Universit���¤t Munchen Weihenstephan, Germany
National University of Ireland, Ireland

Posters & Accepted Abstracts: J Clin Cell Immunol

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.