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© Research
Project

Innate immunity against Aspergillus fumigatus

Scientific Fields
Diseases
Organisms
Applications
Technique
Starting Date
01
Jul 2015
Status
Ongoing
Members
1

About

Aspergillus fumigatus (A.f.) is an ubiquitous thermophilic, saprophytic filamentous fungus. The inhalation of conidia of A.f. may results in different pulmonary diseases. Allergic bronchopulmonary aspergillosis, aspergilloma and invasive pulmonary aspergillosis (are among the most common and threatening pathologies due to A. fumigatus. Invasive pulmonary aspergillosis is most often fatal among immunocompromised patients. Indeed, A.f. has become today the major fungal air-borne pathogen in terms of morbidity and mortality in developed countries. The purpose of our studies is to better understand the innate immunity against this fungus in the immunocompetent and immunocompromised host. We have previously demonstrated that human, mouse or cell-line alveolar macrophages are able to efficiently phagocytize the conidia of A.f. Internalisation is mediated by the actin network and PI-3 kinases. Once internalized, the conidium is directed toward the phagolysosome. The intracellular phagocytosis of conidia triggers the phosphorylation of ERK and p38 MAP-kinases. Few hours after phagocytosis, the conidium grows isodiametrically. This first step in the process of conidial germination is not inhibited in the cells of an immunocompetent individual. The swelling of conidia occurs concomitantly with the translocation and activation of the transcription factor of NF-kB and the production of proinflammatory cytokines such as TNF? and IL-6. Most importantly, swollen conidia are sensitive to phagocytic killing and an immunocompetent mouse is able to clear all inhaled conidia within 3 days. Under immunosuppression, the inflammatory response is altered and the alveolar macrophages fail to clear the conidia. The germination of inhaled conidia results in a massive hyphal growth invading all the lungs alveoli and vessels. Although a massive infiltration of polymorphonuclear neutrophils is observed at the site of infection, the mycelium overgrowth results in the death of animals within 3 to 4 days.