Function of interferons in murine pulmonary PCM: comparative evaluation of disease severity between control mice and knockouts for IFN-alpha/betaR, IFN-gammaR and IRF-1

Abstract

Dendritic cells (DCs) constitute a link between the innate and adaptive immunity. According to the subclass and activation pattern they may play an important role in regulatory and protective immunological effects to the host. In paracoccidioidomycosis (PCM), the systemic mycosis with highest incidence in Latin America, the role of DCs has been poorly studied, although several lines of work have characterized the main parameters of the adaptive immune response in mild and severe forms of the disease. A previous study has demonstrated that the resistance and susceptibility to Paracoccidioides brasiliensis were associated with different DC subpopulations. In addition, in a work at the University of Massachusetts I could demonstrate that plasmacytoid DCs (pDCs), originally described as the main regulators of viral infections, and developed an effective growth control of Aspergillus fumigatus hyphae. Besides, pDCs were able to externalize their DNA forming extracellular traps-like structures when in contact with the fungus. These data warrant further studies that may increase our understanding about the DCs (myeloid and plasmacytoid) function in human and murine pulmonary PCM. We intend to study the phagocytic and fungicide activity, the cytokine production and antigen-presenting function of DCs against P. brasiliensis. The study will be carried out with cells from healthy donors, as well as cells derived from patients suffering from the adult form of the disease. As a complementary study, experiments will be performed in mice to better understand the role of type I IFN in PCM. Thus, we are going to study several parameters of the immune response of C57BL/6 IFN-abR -deficient and C57BL/6 WT P. brasiliensis infected mice. (AU)