Comparative evaluation of mutational and mRNA expression pattern of pulmonary cytokines after infection with Aspergillus flavus and Aspergillus fumigatus

Abstract

Invasive pulmonary aspergillosis (IPA) is a lethal complication of persistent neutropenia. In the pathogenesis of IPA, proinflammatory cytokines seem to play a key role. Howev er, little progress has been made in comparing the production of pulmonary cytokines in mice with IPA caused by A. fumigatus versus A. flavus at the molecular level. Therefore, it was our aim to investigate the mutational and expression pattern of proinflammatory cytokine encoding genes in the lung of immunocompetent and immunocompromised mice infected with either species. The levels of mutational events and transcription of IL-1β and IL-6 encoding genes in the pulmonary tissues of infected mice (with or without immunosuppression) were compared by means of semi-quantitative polymerase chain reaction and PCR-SSCP. Pulmonary fungal burden and histopathological changes were also assessed. The degree of DNA degredation and amounts of pulmonary IL-1β and IL-6 induced by A. fumigatus were much higher than those produced by A. flavus . The differ ential expressions of cytokines by two species were not associated with any mutational events within the selected sequences of the cytokines encoding genes. Our data may explain why A. fumigatus, but less commonly A. flavus , cause IPA and also confirm the contribution of DNA degradation pattern associated with severe inflammation to the pathogenesis of IPA.