Estudo da interação entre o fungo Cryptococcus gattii e a bactéria Streptococcus pneumoniae em modelo murino

Abstract

Cryptococcus gattii (C. gattii) and Streptococcus pneumoniae (S. pneumoniae) are microorganisms that can cause pneumonia, reach several organs, and the Central Nervous System (CNS) causing meningitis and possibly leading to death. The present paper has the objective to characterize the coinfection of S. pneumoniae and C. gattii in a murine model. The results demonstrated that, in a coinfection process with C. gattii, the secondary infection caused by S. pneumoniae significantly worsens the neuropsychiatric state, motor behavior, and autonomous function of the animals, leading to an early death. These results were associated with an increase in bacterial translocation from the lung to other organs, including the central nervous system and the retention of C. gattii in the alveolar infiltrates and lung parenchyma. This site, was verified the high influx of neutrophils and macrophages, increased levels of pro-inflammatory cytokine secretion such as TNF, IFN-γ, IL-17, IL-12p70, mainly IL-1β. Also, pulmonary histopathological lesions and a significant increment in the expression of the platelet aggregating factor receptor (PAFR) were observed in the lung parenchyma, which may be associated with inflammatory intensification and also with increased bacterial translocation to the CNS. At the moment, histopathological studies, a murine knockout model of PAFR, and animal treatment with an IL-1β inhibitor are ongoing to provide a better understanding of the mechanisms that lead to the observed phenotype. These results point to the importance of studying co-infections between microorganisms from different kingdoms, to provide unprecedented knowledge about the progression of polymicrobial diseases.