Abstract
Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in most Latin American countries, especially in Brazil. It is caused by the thermo-dimorphic fungus of the genus Paracoccidioides (Paracoccidioides brasiliensis and Paracoccidioides lutzii). Innate immune response plays a crucial role in host defense against fungal infections, and neutrophils (PMNs) are able to combat microorganisms with three different mechanisms: phagocytosis, secretion of granular proteins, which have antimicrobial properties, and the most recent described mechanism called NETosis. This new process is characterized by the release of net-like structures called Neutrophil Extracellular Traps (NETs), which is composed of nuclear (decondensed DNA and histones) and granular material such as elastase. Several microorganisms have the ability of inducing NETs formation, including gram-positive and gram-negative bacteria, viruses and some fungi. We proposed to identify NETs in tegumentary lesions of patients with PCM and to analyze the interaction between two strains of P. brasiliensis and human PMNs by NETs formation in vitro. In this context, the presence of NETs in vivo was evidenced in tegumentary lesions of patients with PCM by confocal spectrum analyzer. Furthermore, we showed that the high virulent P. brasiliensis strain 18 (Pb18) and the lower virulent strain Pb265 are able to induce different patterns of NETs formation in vitro. The quantification of extracellular DNA corroborates the idea of the ability of P. brasiliensis in inducing NETs release. In conclusion, our data show for the first time the identification of NETs in lesions of patients with PCM and demonstrate distinct patterns of NETs in cultures challenged with fungi in vitro. The presence of NETs components both in vivo and in vitro open new possibilities for the detailed investigation of immunity in PCM.
Highlights
Paracoccidioidomycosis (PCM) is a systemic mycosis considered an important cause of mortality and morbidity in most Latin American countries, especially in Brazil
Studies are focusing on neutrophils’ (PMNs) actions against P. brasiliensis, due to the capacity of these cells to develop different defense strategies against pathogens. and especially due to constant presence of inflammatory infiltrates full of PMNs in the granuloma of the disease
As PMN release of both granular and nuclear material, identified as Neutrophil Extracellular Traps (NETs), is a spectacular action mechanism against microbes, we seek to identify whether this process would be an important mechanism triggered against P. brasiliensis
Summary
Paracoccidioidomycosis (PCM) is a systemic mycosis considered an important cause of mortality and morbidity in most Latin American countries, especially in Brazil. Sporadic cases have been reported in European countries, United States of America (USA) and Japan, in individuals coming from endemic areas [1,2,3,4,5] It is caused by the fungi of the genus Paracoccidioides (Paracoccidioides brasiliensis and Paracoccidioides lutzii) [6,7], which share the same thermodimorphic features, developing as mycelium at room temperature and as yeast at body temperature [8,9]. Innate immune response is essential during early stages of fungal infections [12] Phagocytic cells, such as neutrophils (PMNs) and macrophages, play crucial role in host defense, modulating the inflammatory response and fungicidal activity against P. brasiliensis [12,13,14,15,16,17]. Studies have focused on the role of PMNs during PCM, since a massive infiltration of these cells is found in granulomas of the disease, after chemoattraction modulated by keratinocyte chemoattractant (KC) and macrophage inflammatory protein 1 alpha (MIP-1α) [18]
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