Neutrophils in oral paracoccidioidomycosis and the involvement of Nrf2

PLoS One. 2013 Oct 24;8(10):e76976. doi: 10.1371/journal.pone.0076976. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • Cell Nucleus / metabolism
  • Granuloma / immunology
  • Granuloma / metabolism
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunohistochemistry
  • Mouth / immunology
  • Mouth / microbiology
  • Mouth / pathology
  • NF-E2-Related Factor 2 / immunology*
  • NF-E2-Related Factor 2 / metabolism
  • Neutrophils / immunology*
  • Neutrophils / microbiology
  • Paracoccidioides / immunology*
  • Paracoccidioides / physiology
  • Paracoccidioidomycosis / immunology*
  • Paracoccidioidomycosis / microbiology
  • Paracoccidioidomycosis / pathology

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human

Grants and funding

The authors thank the Brazilian Agencies Fundação de Amparo à Pesquisa do Estado de São Paulo and Conselho Nacional de Desenvolvimento Científico e Tecnológico for the financial support (473939/2011-8). URL: www.cnpq.br. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.