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Mediators of Inflammation
Volume 2016, Article ID 5813794, 13 pages
http://dx.doi.org/10.1155/2016/5813794
Research Article

Protective Effect of Galectin-1 during Histoplasma capsulatum Infection Is Associated with Prostaglandin E2 and Nitric Oxide Modulation

1Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), 14040-903 Ribeirão Preto, SP, Brazil
2Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), 14801-902 Araraquara, SP, Brazil
3Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), 14049-900 Ribeirão Preto, SP, Brazil
4Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
5Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA

Received 16 April 2016; Revised 27 July 2016; Accepted 1 August 2016

Academic Editor: Marc Pouliot

Copyright © 2016 Lílian Cataldi Rodrigues et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Histoplasma capsulatum 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 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 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 PGE2 as an important lipid mediator in the pathogenesis of histoplasmosis.