Estudo da interação entre três diferentes reinos: entendendo a complexidade de co-infecções entre bactérias e o fungo Cryptococcus gattii em modelo murino

Abstract

Cryptococcosis is a mycosis caused by yeasts of the genus Cryptococcus, Considered worldwide as the fifth most lethal infectious disease. It can occur concurrently with other pathogens, characterizing co-infection. Pseudomonas aeruginosa (Pa) and Staphylococcus aureus (Sa) are opportunistic pathogens, causing pneumonia. In this work, the progression of murine cryptococcosis caused by C. gattii (Cg) was evaluated during co-infection with Pa and co-infection with Sa. In vitro analyzes showed that products secreted by different strains of Pa showed an inhibitory activity on the growth of Cg, the same did not occur when Sa was tested. In vivo analyzes, evaluating the morbidity and mortality profile of animals co-infected with Pa X Cg and Sa X Cg, showed a delay in the lethality of animals previously infected with one of the bacteria (Pa + Cg or Sa + Cg groups) when compared with infected animals only with Cg. These changes can be explained by the reduction of the fungal load in the lungs observed in the Pa + Cg or Sa + Cg groups, which led to a delay in the translocation of Cg to the CNS. In co-infection with Pa, these findings were associated with increased recruitment of macrophages and neutrophils producing iNOS in the lung, in addition to mediators such as IL-1β, CXCL-1 and IL-10, resulting in greater macrophage fungicidal activity. The role of the iNOS enzyme in the process was confirmed when the protective phenotype of Pa was reversed in animals treated with an enzyme inhibitor. In Sa co-infection, changes in the cellular recruitment profile in the lungs were also observed. These data revealed that the alteration of the initial Cg installation environment, hindered the spread and transmigration of the fungus to the CNS.