title: Haemophilus influenzae porin induces Toll-like receptor 2-mediated cytokine production in human monocytes and mouse macrophages.
abstract: The production of proinflammatory cytokines is likely to play a major pathophysiological role in meningitis and other infections caused by Haemophilus influenzae type b (Hib). Previous studies have shown that Hib porin contributes to signaling of the inflammatory cascade. We examined here the role of Toll-like receptors (TLRs) and the TLR-associated adaptor protein MyD88 in Hib porin-induced production of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Hib porin-induced TNF-alpha and IL-6 production was virtually eliminated in macrophages from TLR2- or MyD88-deficient mice. In contrast, macrophages from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, which are defective in TLR4 function, responded normally to Hib porin. Moreover anti-TLR2 antibodies but not anti-TLR4 antibodies significantly reduced Hib porin-stimulated TNF-alpha and IL-6 release from the human monocytic cell line THP-1. These data indicate that the TLR2/MyD88 pathway plays an essential role in Hib porin-mediated cytokine production. These findings may be useful in the development of alternative therapies aimed at reducing excessive inflammatory responses during Hib infections.
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione di Microbiologia e Microbiologia Clinica, Seconda Università degli Studi di Napoli, 80138 Naples, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Galdiero
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Galdiero
authors.forename: Emiliana
authors.initials: E
authors.lastname: Finamore
authors.forename: Fabio
authors.initials: F
authors.lastname: Rossano
authors.forename: Maria
authors.initials: M
authors.lastname: Gambuzza
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Catania
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Teti
authors.forename: Angelina
authors.initials: A
authors.lastname: Midiri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancuso
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000502:physiology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D006193:Haemophilus influenzae / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000502:physiology; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88; D018272:Porins / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D018272:Porins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha