title: Protective Effect of Galectin-1 duringHistoplasma capsulatumInfection Is Associated with Prostaglandin E2and Nitric Oxide Modulation.
abstract: Histoplasma capsulatumis a dimorphic fungus that develops a yeast-like morphology in host's tissue, responsible for the pulmonary disease histoplasmosis. The recent increase in the incidence of histoplasmosis in immunocompromised patients highlights the need of understanding immunological controls of fungal infections. Here, we describe our discovery of the role of endogenous galectin-1 (Gal-1) in the immune pathophysiology of experimental histoplasmosis. All infected wild-type (WT) mice survived while only 1/3 of Lgals1-/-mice genetically deficient in Gal-1 survived 30 days after infection. Although infected Lgals1-/-mice had increased proinflammatory cytokines, nitric oxide (NO), and elevations in neutrophil pulmonary infiltration, they presented higher fungal load in lungs and spleen. Infected lung and infected macrophages from Lgals1-/-mice exhibited elevated levels of prostaglandin E2(PGE2, a prostanoid regulator of macrophage activation) and prostaglandin E synthase 2 (Ptgs2) mRNA. Gal-1 did not bind to cell surface of yeast phase ofH. capsulatum,in vitro, suggesting that Gal-1 contributed to phagocytes response to infection rather than directly killing the yeast. The data provides the first demonstration of endogenous Gal-1 in the protective immune response againstH. capsulatumassociated with NO and PGE2as an important lipid mediator in the pathogenesis of histoplasmosis.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Lílian Cataldi
authors.identifier: 0000-0002-2014-2263
authors.initials: LC
authors.lastname: Rodrigues
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Secatto
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Sorgi
authors.affiliation: Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), 14801-902 Araraquara, SP, Brazil.
authors.forename: Naiara N
authors.identifier: 0000-0001-9818-1572
authors.initials: NN
authors.lastname: Dejani
authors.affiliation: Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), 14801-902 Araraquara, SP, Brazil.
authors.forename: Alexandra I
authors.identifier: 0000-0001-6048-3647
authors.initials: AI
authors.lastname: Medeiros
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Morgana Kelly Borges
authors.initials: MK
authors.lastname: Prado
authors.affiliation: Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Simone Gusmão
authors.initials: SG
authors.lastname: Ramos
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cummings
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Stowell
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Lúcia Helena
authors.identifier: 0000-0002-4999-8305
authors.initials: LH
authors.lastname: Faccioli
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Marcelo
authors.identifier: 0000-0002-2039-1884
authors.initials: M
authors.lastname: Dias-Baruffi
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005434:Flow Cytometry; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D006658:Histoplasma / Q000472:pathogenicity*; D006660:Histoplasmosis / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*
chemical_list: D016207:Cytokines; D037483:Galectin 1; D009569:Nitric Oxide; D015232:Dinoprostone