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Mediators of Inflammation
Volume 2015, Article ID 430525, 10 pages
http://dx.doi.org/10.1155/2015/430525
Research Article

Resistance to P. brasiliensis Experimental Infection of Inbred Mice Is Associated with an Efficient Neutrophil Mobilization and Activation by Mediators of Inflammation

1Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (UNIFAL), Brazil
2Setor de Ciências da Saúde, Universidade Federal do Paraná (UFPR), Brazil
3Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), Brazil

Received 3 July 2015; Revised 21 October 2015; Accepted 25 October 2015

Academic Editor: Helen C. Steel

Copyright © 2015 Felipe Fornias Sperandio et al. This 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.

Abstract

Paracoccidioidomycosis (PCM) is a systemic fungal infection, endemic in Brazil, that leads to severe morbidity and even mortality if not correctly treated. Patients may respond differently to PCM depending on the pattern of the acquired immune response developed. The onset of protective immune response is notably mediated by neutrophils (PMN) that play an important role through directly killing the fungi and also by interacting with other cell types to modulate the acquired protective immune response that may follow. In that way, this study aimed to present and compare different experimental models of PCM (intraperitoneal and subcutaneous) regarding PMN production and maturation inside femoral bone marrow and also PMN infiltration in peritoneal and subcutaneous exudates of resistant and susceptible mice. We also assessed the fungal colony forming units and the levels of soluble inflammatory mediators (LTB4, KC, IFN-γ, GM-CSF, and IL-10) inside subcutaneous air-pouches to compare the efficiency of the PMN present at this site in relation to the two main neutrophil functions: initial lysis of the invading pathogen and modulation of the acquired immune response. P. brasiliensis inoculated intraperitoneally was able to disseminate to the bone marrow of susceptible mice, causing a more marked alteration of PMN production and maturation than that observed after resistant mice infection by the same route. Subcutaneous air-pouch inoculation of P. brasiliensis elicited a controlled and limited infection that produced a PMN-rich exudate, thus favoring the study of the interaction between the fungus and the neutrophils. Susceptible mice produced higher numbers of PMN; however, these cells were less effective in killing the fungi. Inflammatory cytokines were more pronounced in resistant mice, which supports their PCM raised resistance.