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

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Rodrigues, Lilian Cataldi ; Secatto, Adriana ; Sorgi, Carlos A. ; Dejani, Naiara N. ; Medeiros, Alexandra I. ; Borges Prado, Morgana Kelly ; Ramos, Simone Gusmao ; Cummings, Richard D. ; Stowell, Sean R. ; Faccioli, Locia Helena ; Dias-Baruffi, Marcelo

• Document type: Journal article
• Source: Mediators of Inflammation; 2016.
• Web of Science Citations: 1

Abstract

Histoplasma capsulatum is a dimorphic fungus that develops a yeast-likemorphology 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-2 (PGE(2), a prostanoid regulator of macrophage activation) and prostaglandin E synthase 2 (Ptgs2) mRNA. Gal-1 did not bind to cell surface of yeast phase of H. 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 against H. capsulatum associated with NO and PGE(2) as an important lipid mediator in the pathogenesis of histoplasmosis. (AU)

• FAPESP's process: 11/17611-7 - Effect of efferocytosis by dendritic cells on Th17 differentiation: role of Prostaglandin E2
• Grantee: Alexandra Ivo de Medeiros
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 07/02487-3 - Study of the mechanism of action of coumarin derivatives on the myeloperoxidase activity: investigation about metabolization of these compounds to phenoxyl free radicals, implications on the oxidative stress and modulation of leukocyte functions
• Grantee: Yara Maria Lucisano Valim
• Support Opportunities: Regular Research Grants
• FAPESP's process: 07/00840-8 - Study of the mechanism of action of coumarin derivatives on the myeloperoxidase activity: investigation about metabolization of these compounds to phenoxyl free radicals, implications on the oxidative stress and modulation of leukocyte functions
• Grantee: Luciana Mariko Kabeya
• Support Opportunities: Scholarships in Brazil - Post-Doctorate