title: NO is a macrophage autonomous modifier of the cytokine response to streptococcal single-stranded RNA.
abstract: Group B streptococci, a major cause of sepsis, induce inflammatory cytokines in strict dependence on bacterial ssRNA and the host molecules MyD88 and UNC-93B. In this study, we show that NO plays an important role in Group B streptococci-induced transcriptional activation of cytokine genes. Phagocytosis induced NO in a MyD88-dependent fashion. In turn, NO propagated the acidification of phagosomes and the processing of phagosomal bacterial nucleic acids and was required for potent transcriptional activation of cytokine genes by streptococci. This NO-dependent amplification loop has important mechanistic implications for the anti-streptococcal macrophage response and sepsis pathogenesis.
authors.affiliation: Center of Chronic Immunodeficiency, University of Freiburg, 79106 Freiburg, Germany. Sachin.Deshmukh@uniklinik-freiburg.de
authors.forename: Sachin D
authors.initials: SD
authors.lastname: Deshmukh
authors.forename: Sabrina
authors.initials: S
authors.lastname: Müller
authors.forename: Katrin
authors.initials: K
authors.lastname: Hese
authors.forename: Katharina S
authors.initials: KS
authors.lastname: Rauch
authors.forename: Julia
authors.initials: J
authors.lastname: Wennekamp
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
authors.forename: Philipp
authors.initials: P
authors.lastname: Henneke
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007231:Infant, Newborn; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency / Q000235:genetics; D010587:Phagocytosis / Q000276:immunology; D010588:Phagosomes / Q000276:immunology / Q000382:microbiology; D012323:RNA Processing, Post-Transcriptional / Q000276:immunology*; D012329:RNA, Bacterial / Q000378:metabolism*; D013292:Streptococcus agalactiae / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012329:RNA, Bacterial; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II