title: Immunoevasive Aspergillus virulence factors.
abstract: Individuals with structural lung disease or defective immunity are predisposed to Aspergillus-associated disease. Manifestations range from allergic to cavitary or angio-invasive syndromes. Despite daily spore inhalation, immunocompetence facilitates clearance through initiation of innate and adaptive host responses. These include mechanical barriers, phagocyte activation, antimicrobial peptide release and pattern recognition receptor activation. Adaptive responses include Th1 and Th2 approaches. Understanding Aspergillus virulence mechanisms remains critical to the development of effective research and treatment strategies to counteract the fungi. Major virulence factors relate to fungal structure, protease release and allergens; however, mechanisms utilized to evade immune recognition continue to be important in establishing infection. These include the fungal rodlet layer, dihydroxynaphthalene-melanin, detoxifying systems for reactive oxygen species and toxin release. One major immunoevasive toxin, gliotoxin, plays a key role in mediating Aspergillus-associated colonization in the context of cystic fibrosis. Here, it down-regulates vitamin D receptor expression which following itraconazole therapy is rescued concurrent with decreased Th2 cytokine (IL-5 and IL-13) concentrations in the CF airway. This review focuses on the interaction between Aspergillus pathogenic mechanisms, host immune responses and the immunoevasive strategies employed by the organism during disease states such as that observed in cystic fibrosis.
authors: Department of Medicine, Education and Research Centre, Beaumont Hospital, Royal College of Surgeons in Ireland, Beaumont Road, Dublin 9, Republic of Ireland, schotirmall@rcsi.ie.
authors: Sanjay H
authors: SH
authors: Chotirmall
authors: Bojana
authors: B
authors: Mirkovic
authors: Gillian M
authors: GM
authors: Lavelle
authors: Noel G
authors: NG
authors: McElvaney
mesh_terms: D001228:Aspergillosis / Q000276:immunology* / Q000382:microbiology*; D001230:Aspergillus / Q000254:growth & development* / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D037521:Virulence Factors