title: Signaling via the MyD88 adaptor protein in B cells suppresses protective immunity during Salmonella typhimurium infection.
abstract: The myeloid differentiation primary response gene 88 (Myd88) is critical for protection against pathogens. However, we demonstrate here that MyD88 expression in B cells inhibits resistance of mice to Salmonella typhimurium infection. Selective deficiency of Myd88 in B cells improved control of bacterial replication and prolonged survival of the infected mice. The B cell-mediated suppressive pathway was even more striking after secondary challenge. Upon vaccination, mice lacking Myd88 in B cells became completely resistant against this otherwise lethal infection, whereas control mice were only partially protected. Analysis of immune defenses revealed that MyD88 signaling in B cells suppressed three crucial arms of protective immunity: neutrophils, natural killer cells, and inflammatory T cells. We further show that interleukin-10 is an essential mediator of these inhibitory functions of B cells. Collectively, our data identify a role for MyD88 and B cells in regulation of cellular mechanisms of protective immunity during infection.
authors.affiliation: Deutsches Rheuma-Forshungszentrum, a Leibniz institute, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Neves
authors.forename: Vicky
authors.initials: V
authors.lastname: Lampropoulou
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Calderon-Gomez
authors.forename: Toralf
authors.initials: T
authors.lastname: Roch
authors.forename: Ulrik
authors.initials: U
authors.lastname: Stervbo
authors.forename: Ping
authors.initials: P
authors.lastname: Shen
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Matthias
authors.initials: M
authors.lastname: Haury
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Nedospasov
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Steinhoff
authors.forename: Dinis P
authors.initials: DP
authors.lastname: Calado
authors.forename: Simon
authors.initials: S
authors.lastname: Fillatreau
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D012481:Salmonella Infections, Animal / Q000276:immunology*; D022562:Salmonella Vaccines / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D022562:Salmonella Vaccines; D016753:Interleukin-10