Modelo de pneumonia intersticial causada pelo Encephalitozoon cuniculi em camundongos

Abstract

Pneumonias are important conditions that impact the survival of immunosuppressed and immunocompromised patients. Encephalitozoon cuniculi is an obligate intracellular pathogen that infects vertebrate hosts, including humans, and is opportunistic in most infections. The occurrence of encephalitozoonosis-related pneumonia has been rarely reported. Thus, the aim of this study was to characterize pneumonia in mice treated or not with cyclophosphamide (Cy) and experimentally infected with Encephalitozoon cuniculi, to establish an animal model of opportunistic fungal pneumonia. C57BL/6 mice, males, aged 6-8 weeks, were infected intravenously with E. cuniculi spores and treated with Cy (75 mg/kg/week, intraperitoneally). Controls were uninfected and untreated. Thirty days post-infection, fungal load (qPCR), histopathological lesions, cytokine production, and the phenotype of the immune cells present in the parenchyma were evaluated from lung tissue by flow cytometry. Histologically, interstitial pneumonia with lymphocytic infiltrate was observed in the infected animals. This infiltrate consisted mainly of T CD8+ and CD4+ lymphocytes, and B lymphocyte and macrophage populations were reduced. Fungal load was higher in the Cy-treated animals, which was confirmed by immunohistochemistry, with visualization of spores in lung tissue. These results demonstrate that C57BL/6 mice treated or not with Cy and infected with E. cuniculi had lymphocytic interstitial pneumonia, aggravated by immunosuppression. This model may be used to study opportunistic fungal pneumonias.