title: Disruption of CD40-CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection.
abstract: To study the role of CD40 ligand (CD40L) in the host immune responses against intracellular pathogens, we infected CD40L knockout (CD40L-/-) mice with Leishmania amazonensis. Although wild-type mice were susceptible to infection and developed progressive ulcerative lesions, tissue parasite burdens in CD40L-/- mice were significantly higher. This heightened susceptibility to infection was associated with an impaired T cell and macrophage activation and altered inflammatory response, as reflected by low levels of IFN gamma, lymphotoxin-tumor necrosis factor (LT-TNF), and nitric oxide (NO) production. Furthermore, CD40L-/- mice failed to generate a protective immune response after immunization. These results indicate an essential role of cognate CD40-CD40L interactions in the generation of cellular immune responses against an intracellular parasite.
authors.affiliation: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.
authors.forename: L
authors.initials: L
authors.lastname: Soong
authors.forename: J C
authors.initials: JC
authors.lastname: Xu
authors.forename: I S
authors.initials: IS
authors.lastname: Grewal
authors.forename: P
authors.initials: P
authors.lastname: Kima
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: B J
authors.initials: BJ
authors.lastname: Longley
authors.forename: N H
authors.initials: NH
authors.lastname: Ruddle
authors.forename: D
authors.initials: D
authors.lastname: McMahon-Pratt
authors.forename: R A
authors.initials: RA
authors.lastname: Flavell
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D004198:Disease Susceptibility; D006790:Host-Parasite Interactions; D007894:Leishmania mexicana / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology; D008024:Ligands; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009569:Nitric Oxide / Q000096:biosynthesis
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D009569:Nitric Oxide