title: CD40 signaling induces reciprocal outcomes in Leishmania-infected macrophages; roles of host genotype and cytokine milieu.
abstract: We investigated the influence of CD40-CD40 ligand-mediated signaling on induction of microbicidal activity against Leishmania major in macrophages from resistant (B6) and susceptible (BALB) mouse strains. CD40 engagement induced leishmanicidal activity in resistant macrophages, but increased parasite replication in susceptible macrophages. CD40 engagement induced comparable TNF-alpha production in macrophages from both strains. However, increased IL-10 production was restricted to susceptible macrophages. Increased parasite replication in susceptible macrophages was prevented by a neutralizing anti-IL-10 antibody. In the presence of IFN-gamma, CD40 engagement induced Leishmania killing by macrophages from both strains. Therefore, the outcome of CD40 signaling on effector responses against L. major depends on host genotype and the cytokine milieu, and a source of IFN-gamma is required for a protective response.
authors.affiliation: Instituto Oswaldo Cruz, FIOCRUZ, Avenida Brasil, 4365, Rio de Janeiro, RJ, 21045-900, Brazil.
authors.forename: Marise P
authors.initials: MP
authors.lastname: Nunes
authors.forename: Lea
authors.initials: L
authors.lastname: Cysne-Finkelstein
authors.forename: Bruna C
authors.initials: BC
authors.lastname: Monteiro
authors.forename: Daniel M
authors.initials: DM
authors.lastname: de Souza
authors.forename: Nitza A
authors.initials: NA
authors.lastname: Gomes
authors.forename: George A
authors.initials: GA
authors.lastname: DosReis
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D020022:Genetic Predisposition to Disease; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology*; D007896:Leishmaniasis / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000187:drug effects; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D019013:CD40 Antigens; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma