Research Article
Protective Effect of Galectin-1 during
Histoplasma capsulatum Infection Is Associated with
Prostaglandin E
2
and Nitric Oxide Modulation
Lílian Cataldi Rodrigues,
1
Adriana Secatto,
1
Carlos A. Sorgi,
1
Naiara N. Dejani,
2
Alexandra I. Medeiros,
2
Morgana Kelly Borges Prado,
1
Simone Gusmão Ramos,
3
Richard D. Cummings,
4
Sean R. Stowell,
5
Lúcia Helena Faccioli,
1
and Marcelo Dias-Baruffi
1
1
Departamento de An´ alises Cl´ ınicas, Toxicol´ ogicas e Bromatol´ ogicas, Faculdade de Ciˆ encias Farmacˆ euticas de Ribeir˜ ao Preto,
Universidade de S˜ ao Paulo (USP), 14040-903 Ribeir˜ ao Preto, SP, Brazil
2
Departamento de Ciˆ encias Biol´ ogicas, Faculdade de Ciˆ encias Farmacˆ euticas, Universidade Estadual Paulista (UNESP),
14801-902 Araraquara, SP, Brazil
3
Departamento de Patologia, Faculdade de Medicina de Ribeir˜ ao Preto, Universidade de S˜ ao Paulo (USP),
14049-900 Ribeir˜ ao Preto, SP, Brazil
4
Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
5
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA
Correspondence should be addressed to Marcelo Dias-Baruf; mdbaruf@fcfrp.usp.br
Received 16 April 2016; Revised 27 July 2016; Accepted 1 August 2016
Academic Editor: Marc Pouliot
Copyright © 2016 L´ ılian Cataldi Rodrigues et al. Tis 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.
Histoplasma capsulatum is a dimorphic fungus that develops a yeast-like morphology in host’s tissue, responsible for the pulmonary
disease histoplasmosis. Te 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 defcient in Gal-1 survived 30 days afer infection. Although infected Lgals1
−/−
mice had increased
proinfammatory cytokines, nitric oxide (NO), and elevations in neutrophil pulmonary infltration, 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. Te data provides the frst 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.
1. Introduction
Histoplasmosis is a worldwide known disease caused by
the fungus Histoplasma capsulatum. Te real geographic
distribution of this mycosis could be more widespread than
what was previously thought [1, 2]. Te incidence of this
fungal disease is higher in the Mid- and Southeast USA,
Latin America, China, and other world areas [2]. Addition-
ally, asymptomatic cases are escalating and are reported to
predominately afect immunocompromised individuals as an
acute pulmonary infection similar to mild fu-like symptoms
[1, 3, 4]. Likewise, the most severe symptomatic form of the
disease, referred to as disseminated histoplasmosis, develops
most commonly in immunosuppressed patients. However,
unlike the mild form, disseminated histoplasmosis can lead
to death [4]. Although antifungal therapies have been used
against the fungus, there are no current alternative therapies
to treat or protect against H. capsulatum infection.
H. capsulatum is a dimorphic, facultative, intracellular
pathogen found as a yeast phase when in host tissue [5].
Hindawi Publishing Corporation
Mediators of Inflammation
Volume 2016, Article ID 5813794, 13 pages
http://dx.doi.org/10.1155/2016/5813794