Abstract

Neutrophils have been implicated in granuloma formation in several infectious diseases, in addition to their main phagocytic and pathogen destruction role. It has been demonstrated that Nrf2 regulates antioxidant protection in neutrophils, attenuating inflammation without compromising the hosts bacterial defense. In this study, we analyzed the presence of neutrophils in Paracoccidioides brasiliensis mycosis (PCM), as well as the immunoexpression of Nrf2. Thirty-nine cases of oral PCM were classified according to quantity of fungi and to the presence of loose or well-organized granulomas and microabscesses. An Nrf2 antibody was used for immunohistochemical analysis. The results showed that neutrophils are present in microabscesses and loose granulomas, but were absent in structured granulomas. A greater quantity of fungi was shown in cases with only loose granulomas when compared to loose and well organized granulomas. Nrf2 was observed in the nuclei of neutrophils of loose granulomas and abscesses, with its expression in loose granulomas maintained despite the additional presence of well organized granulomas in the same specimen. This study suggests that neutrophils participate in P. brasiliensis granuloma formation and that Nrf2 has a possible role in neutrophil survival, via modulation of the inflammatory response.

Highlights

  • Paracoccidioidomycosis (PCM) is known to be one of the most frequent systemic fungal infections affecting the rural population of Latin America, predominantly in Brazil

  • We observed that neutrophils were present in both microabscesses and loose granulomas, and absent in well-organized granulomas (Figures 1A, 1C, 1E)

  • We have focused on the presence of neutrophils in the inflammatory response induced by the presence of the fungus P. brasiliensis

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Summary

Introduction

Paracoccidioidomycosis (PCM) is known to be one of the most frequent systemic fungal infections affecting the rural population of Latin America, predominantly in Brazil. The neutrophils are replaced by macrophages and multinucleated giant cells, followed by epithelioid cells. These cells are concomitantly found within the formation of a mononuclear cell halo. Of varying intensity, is generally seen surrounding the granuloma, which is gradually replaced by fibrous scar tissue [2]. This morphology is normally seen in a well-organized granuloma, depending on the immunological response of the host, it may be observed in ill-defined granuloma, or so-called loose granuloma (Figure S1)

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