About
Agostinho CARVALHO –University of Minho – Portugal
Recent progress in medical care has, paradoxically, contributed to an increased prevalence of life-threatening susceptibility to severe forms of fungal infection, such as invasive pulmonary aspergillosis (IPA), caused primarily by the opportunistic fungus Aspergillus fumigatus. Despite remarkable progress in the diagnosis and treatment of IPA, it remains a leading cause of morbidity and mortality among immunocompromised hosts. Given the variable risk of infection and its clinical outcome even among patients with comparable predisposing clinical factors and microbiological exposure, susceptibility to IPA is thought to rely largely on genetic predisposition. Protection against fungi is conferred mainly through phagocytes that recognize pathogen motifs through pattern recognition receptors. The fungal cell wall is the main source of motifs owing to its dynamic composition and structural properties according to morphotype, growth stage and environmental conditions. Over the past years, we have been exploring human genetic variation in innate immune receptors as a tool to dissect the molecular and cellular mechanisms that regulate the activation of antifungal immunity, and whose impairment predisposes to fungal disease. Relevant examples include the C-type lectin receptor Dectin-1 and the pattern recognition molecule pentraxin-3 (PTX3). Although the overall weight of the antifungal immune response results from adding effects of single genetic factors and their complex interactions with clinical immune dysfunctions, several genetic targets have been recently validated as robust markers of susceptibility to fungal disease. These findings are now expected to lay the foundations for prospective trials, ultimately endorsing genetic testing in personalized medical interventions for IPA
Link to your website:
http://www.icvs.uminho.pt/research-scientists/microbiology-infection/people/agostinhocarvalho
Contact : Timea MARTON (timea.marton@pasteur.fr Poste : 31 26)