Antibodies Against Glycolipids Enhance Antifungal Activity of Macrophages and Reduce Fungal Burden After Infection with Paracoccidioides brasiliensis.

Renata A Bueno,Luiz R Travassos,Julian E Muñoz,Carlos P Taborda,Márcia R Pinto,Luciana Thomaz,Joshua D Nosanchuk,Cássia J Da Silva

doi:10.3389/fmicb.2016.00074

Abstract

Paracoccidioidomycosis is a fungal disease endemic in Latin America. Polyclonal antibodies to acidic glycosphingolipids (GSLs) from Paracoccidioides brasiliensis opsonized yeast forms in vitro increasing phagocytosis and reduced the fungal burden of infected animals. Antibodies to GSL were active in both prophylactic and therapeutic protocols using a murine intratracheal infection model. Pathological examination of the lungs of animals treated with antibodies to GSL showed well-organized granulomas and minimally damaged parenchyma compared to the untreated control. Murine peritoneal macrophages activated by IFN-γ and incubated with antibodies against acidic GSLs more effectively phagocytosed and killed P. brasiliensis yeast cells as well as produced more nitric oxide compared to controls. The present work discloses a novel target of protective antibodies against P. brasiliensis adding to other well-studied mediators of the immune response to this fungus.

Highlights

The agents of Paracoccidioidomycosis (PCM) are a complex group of fungi within the Paracoccidioides genus comprised of four distinct phylogenetic lineages known as PS2, PS3, S1, and Pb01-like (Matute et al, 2006; Teixeira et al, 2009)
The capacity of J774.16 macrophage-like cells for the phagocytosis of P. brasiliensis yeast was assessed using different conditions in 6, 12, and 24 h co-cultures with macrophages activated by IFN-γ 24 h before the assays
It is noteworthy that the total serum contains various kinds of antibodies, against GSL, and that these antibodies might induce macrophage-like phagocytosis of P. brasiliensis yeasts

Summary

Introduction

The agents of Paracoccidioidomycosis (PCM) are a complex group of fungi within the Paracoccidioides genus comprised of four distinct phylogenetic lineages known as PS2, PS3, S1, and Pb01-like (Matute et al, 2006; Teixeira et al, 2009). PCM is a systemic granulomatous disease initiated by the inhalation of Paracoccidioides sp. Conidia that subsequently transform into yeast forms in the lungs. Grows in the yeast form at human physiological temperature and in the mycelial form at 25◦C (Franco et al, 1993). PCM is endemic in a broad region from Mexico to Argentina, ∼80% of diagnosed patients are in Brazil. Most patients are rural workers but cases occur in urban centers, especially those located along routes used by migrant workers (Restrepo, 1985; McEwen et al, 1995). PCM is the prevalent systemic mycosis in Latin America, with the highest mortality rate among the systemic mycoses in Brazil (Prado et al, 2009)

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