AUTHOR=de Oliveira Stephan Alberto Machado , Reis Janayna Nunes , Catão Elisa , Amaral Andre Correa , Souza Ana Camila Oliveira , Ribeiro Alice Melo , Faccioli Lúcia Helena , Carneiro Fabiana Pirani , Marina Clara Luna Freitas , Bürgel Pedro Henrique , Fernandes Larissa , Tavares Aldo Henrique , Bocca Anamelia Lorenzetti 

TITLE=β2 Integrin-Mediated Susceptibility to Paracoccidioides brasiliensis Experimental Infection in Mice

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.622899

DOI=10.3389/fcimb.2021.622899

ISSN=2235-2988

ABSTRACT=<p>The earliest interaction between macrophages and <italic>Paracoccidioides brasiliensis</italic> is particularly important in paracoccidioidomycosis (PCM) progression, and surface proteins play a central role in this process. The present study investigated the contribution of β2 integrin in <italic>P. brasiliensis</italic>-macrophage interaction and PCM progression. We infected β2-low expression (CD18<sup>low</sup>) and wild type (WT) mice with <italic>P. brasiliensis</italic> 18. Disease progression was evaluated for fungal burden, lung granulomatous lesions, nitrate levels, and serum antibody production. Besides, the <italic>in vitro</italic> capacity of macrophages to internalize and kill fungal yeasts was investigated. Our results revealed that CD18<sup>low</sup> mice infected with Pb18 survived during the time analyzed; their lungs showed fewer granulomas, a lower fungal load, lower levels of nitrate, and production of high levels of IgG1 in comparison to WT animals. Our results revealed that <italic>in vitro</italic> macrophages from CD18<sup>low</sup> mice slowly internalized yeast cells, showing a lower fungal burden compared to WT cells. The migration capacity of macrophages was compromised and showed a higher intensity in the lysosome signal when compared with WT mice. Our data suggest that β2 integrins play an important role in fungal survival inside macrophages, and once phagocytosed, the macrophage may serve as a protective environment for <italic>P. brasiliensis.</italic></p>