Characterization of tissue immune response in post renal transplantation patients with fungal infection caused by the Cryptococcus neoformans / Cryptococcus gattii species complex

Abstract

Yeasts of the Cryptococcus neoformans / C. gattii species complex are an important cause of infection in humans and may cause symptoms of pneumonia and meningoencephalitis in immunocompromised patients or even in immunocompetent patients exposed to the agent. It is estimated that C. neoformans infects almost one million individuals worldwide annually. Cryptococcosis is the second major systemic mycosis related to kidney transplants, which is the most likely group to develop cryptococcosis among solid organ transplant recipients. In 2011, kidney transplants accounted for 72% of all solid organ transplants performed in Brazil. There are few studies reporting the incidence of cryptococcosis in this risk group and correlating the different profiles of immune response during infection and pathogen / host interaction in renal transplant patients. The main objective of this work is to characterize the diversity of the tissue immune response in renal transplant recipients with cryptococcosis, assessing which activation and regulation pathways of the adaptive immune response are being expressed. The casuistic will be formed in collaboration with the Hospital São Paulo (HSP) and the Hospital do Rim e Hipertensão (HRH), composed of 13 patients treated in these hospitals, who had cryptococcal infection during the period from 2005 to 2012. The isolates of C. neoformans / C. gattii complex collected from these patients will be identified by biochemical methods and by DNA sequencing. Paraffin tissue sections from skin and lung biopsies of these same patients will be used for histopathology and immunohistochemistry to evaluate: a) the immunological profile of posttransplant patients analyzing the in situ expression of cytokines and cell population markers of adaptive immune response (regulatory T cells); b) the molecular diversity of the fungus and its relation to the infection sites, identifying the predominant serotype in the group of patients analyzed; c) possible correlations between different tissue responses and previous exposure to immunosuppressive drugs. (AU)