PURPOSE OF REVIEW: Aspergillus fumigatus causes invasive and allergenic disease. Host defense relies on the ability of the respiratory immune system to restrict spore germination into invasive hyphae and to limit fungus-induced or inflammation-induced damage in infected tissues. This review covers the molecular and cellular events that mediate innate and CD4 T-cell responses to A. fumigatus and fungal attributes that counter hostile microenvironments and, in turn, affect host responses. RECENT FINDINGS: Host recognition of fungal cell wall components is critical for fungal uptake, killing, and the formation of protective innate and CD4 T-cell effector populations. Beyond the known role of neutrophils and macrophages, circulating monocytes, dendritic cells, and natural killer cells contribute to optimal defense against A. fumigatus. Genetic and pharmacologic manipulation of A. fumigatus reveals that hypoxia adaptation, cell wall assembly, and secondary metabolite production in mammalian tissues contribute to fungal pathogenesis and the outcome of infection. SUMMARY: Greater understanding of the immune mechanisms that underlie protective responses and fungal pathways that promote microbial adaptation and growth in mammalian tissue provide a conceptual framework for improving current antifungal therapies.
PURPOSE OF REVIEW: Aspergillus fumigatus causes invasive and allergenic disease. Host defense relies on the ability of the respiratory immune system to restrict spore germination into invasive hyphae and to limit fungus-induced or inflammation-induced damage in infected tissues. This review covers the molecular and cellular events that mediate innate and CD4 T-cell responses to A. fumigatus and fungal attributes that counter hostile microenvironments and, in turn, affect host responses. RECENT FINDINGS: Host recognition of fungal cell wall components is critical for fungal uptake, killing, and the formation of protective innate and CD4 T-cell effector populations. Beyond the known role of neutrophils and macrophages, circulating monocytes, dendritic cells, and natural killer cells contribute to optimal defense against A. fumigatus. Genetic and pharmacologic manipulation of A. fumigatus reveals that hypoxia adaptation, cell wall assembly, and secondary metabolite production in mammalian tissues contribute to fungal pathogenesis and the outcome of infection. SUMMARY: Greater understanding of the immune mechanisms that underlie protective responses and fungal pathways that promote microbial adaptation and growth in mammalian tissue provide a conceptual framework for improving current antifungal therapies.
Authors: Gregory A Lamaris; Russell E Lewis; Georgios Chamilos; Gregory S May; Amar Safdar; Thomas J Walsh; Issam I Raad; Dimitrios P Kontoyiannis Journal: J Infect Dis Date: 2008-07-15 Impact factor: 5.226
Authors: Taylor R T Dagenais; Steve S Giles; Vishukumar Aimanianda; Jean-Paul Latgé; Christina M Hull; Nancy P Keller Journal: Infect Immun Date: 2009-11-16 Impact factor: 3.441
Authors: Nikolaus Rieber; Roel P Gazendam; Alexandra F Freeman; Amy P Hsu; Amanda L Collar; Janyce A Sugui; Rebecca A Drummond; Chokechai Rongkavilit; Kevin Hoffman; Carolyn Henderson; Lily Clark; Markus Mezger; Muthulekha Swamydas; Maik Engeholm; Rebecca Schüle; Bettina Neumayer; Frank Ebel; Constantinos M Mikelis; Stefania Pittaluga; Vinod K Prasad; Anurag Singh; Joshua D Milner; Kelli W Williams; Jean K Lim; Kyung J Kwon-Chung; Steven M Holland; Dominik Hartl; Taco W Kuijpers; Michail S Lionakis Journal: JCI Insight Date: 2016-10-20