title: Evidence for the requirement for CD40-CD154 interactions in resistance to infections with attenuated Salmonella.
abstract: Salmonella species include facultative intracellular pathogens which reside preferentially within cells of the host's reticulo-endothelial system. Resistance to Salmonella involves a collaboration between cells of the innate and adaptive immune systems, and protective immunity requires cell-mediated and humoral-immune responses. CD40-CD154 interactions are of central importance in the induction of cellular immune responses. In the present study, CD154-deficient (CD154(-/-)) mice were used to assess the role of CD40-CD154 interactions in immunity to Salmonella infection. Compared to C57BL/6 (CD154(+/+)) controls, CD154(-/-) mice were hypersusceptible to infection by an attenuated strain of Salmonella enterica serovar Typhimurium (S. typhimurium), as evidenced by a significantly decreased survival rate. CD154(-/-) mice exhibited a defect in the production of IFN-gamma and NO in the acute phase of the disease, which resulted in a failure to control bacterial replication. We conclude that intercellular communications via the CD40-CD154 pathway play a critical role in the induction type-1 cytokine responses and protection against primary infections with attenuated Salmonella.
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Fernandez-Cabezudo
authors.forename: Azim
authors.initials: A
authors.lastname: Ullah
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Basel K
authors.initials: BK
authors.lastname: Al-Ramadi
mesh_terms: D000210:Acute-Phase Reaction / Q000209:etiology; D000818:Animals; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D003470:Culture Media / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D004198:Disease Susceptibility; D007110:Immunity, Active; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D008099:Liver / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000401:mortality*; D012486:Salmonella typhimurium / Q000145:classification / Q000235:genetics / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D012703:Serotyping; D013154:Spleen / Q000166:cytology / Q000382:microbiology; D015996:Survival Rate; D018417:Th1 Cells / Q000276:immunology; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000008:administration & dosage
chemical_list: D019013:CD40 Antigens; D003470:Culture Media; D016207:Cytokines; D014613:Vaccines, Attenuated; D023201:CD40 Ligand; D009569:Nitric Oxide; D007371:Interferon-gamma