Protective Effect of Galectin-1 during Histoplasma capsulatum Infection Is Associated with Prostaglandin E 2 and Nitric Oxide Modulation

• Published in: Mediators of inflammation Vol. 2016; p. 5813794
• Main Authors: Rodrigues, Lílian Cataldi, Secatto, Adriana, Sorgi, Carlos A, Dejani, Naiara N, Medeiros, Alexandra I, Prado, Morgana Kelly Borges, Ramos, Simone Gusmão, Cummings, Richard D, Stowell, Sean R, Faccioli, Lúcia Helena, Dias-Baruffi, Marcelo
• Format: Journal Article
• Language: English
• Published: United States 2016
• Subjects: Animals; Cytokines - metabolism; Dinoprostone - metabolism; Flow Cytometry; Galectin 1 - genetics; Galectin 1 - metabolism; Histoplasma - pathogenicity; Histoplasmosis - metabolism; Histoplasmosis - microbiology; Humans; Lung - metabolism; Lung - microbiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide - metabolism
• ISSN: 1466-1861

is 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 E
(PGE
, a prostanoid regulator of macrophage activation) and prostaglandin E synthase 2 (
) mRNA. Gal-1 did not bind to cell surface of yeast phase of
,
, 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 against
associated with NO and PGE
as an important lipid mediator in the pathogenesis of histoplasmosis.