title: Leukotrienes are potent adjuvant during fungal infection: effects on memory T cells.
abstract: Leukotrienes (LTs) are potent lipid mediators involved in the control of host defense. LTB(4) induces leukocyte accumulation, enhances phagocytosis and bacterial clearance, and increases NO synthesis. LTB(4) is also important in early effector T cell recruitment that is mediated by LTB(4) receptor 1, the high-affinity receptor for LTB(4). The aims of this study were to evaluate whether LTs are involved in the secondary immune response to vaccination in a murine model of Histoplasma capsulatum infection. Our results demonstrate that protection of wild-type mice immunized with cell-free Ags from H. capsulatum against histoplasmosis was associated with increased LTB(4) and IFN-gamma production as well as recruitment of memory T cells into the lungs. In contrast, cell-free Ag-immunized mice lacking 5-lipoxygenase(-/-), a critical enzyme involved in LT synthesis, displayed a marked decrease on recruitment of memory T cells to the lungs associated with increased synthesis of TGF-beta as well as IL-10. Strikingly, these effects were associated with increased mortality to 5-lipoxygenase(-/-)-infected mice. These data establish an important immunomodulatory role of LTs, in both the primary and secondary immune responses to histoplasmosis.
authors.affiliation: Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Alexandra I
authors.initials: AI
authors.lastname: Medeiros
authors.forename: Anderson
authors.initials: A
authors.lastname: Sá-Nunes
authors.forename: Walter M
authors.initials: WM
authors.lastname: Turato
authors.forename: Adriana
authors.initials: A
authors.lastname: Secatto
authors.forename: Fabiani G
authors.initials: FG
authors.lastname: Frantz
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Sorgi
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Serezani
authors.forename: George S
authors.initials: GS
authors.lastname: Deepe
authors.forename: Lúcia H
authors.initials: LH
authors.lastname: Faccioli
mesh_terms: D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D000946:Antigens, Fungal / Q000008:administration & dosage / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology; D006658:Histoplasma / Q000276:immunology; D006660:Histoplasmosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D006801:Humans; D007113:Immunity, Innate; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D008172:Lung Diseases, Fungal / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000382:microbiology
chemical_list: D000276:Adjuvants, Immunologic; D000946:Antigens, Fungal; D016207:Cytokines; D005657:Fungal Vaccines; D007975:Leukotriene B4