Putative virulence factors of Aspergillus fumigatus

Various putative virulence factors of Aspergillus fumigatus have been studied over the past decades. A. fumigatus gliotoxin is a potent inhibitor of the mucociliary system. Several fungal metabolites interfere with phagocytosis and opsonization including toxins, 'conidial inhibitory factor', 'A. fumigatus diffusible product' and 'complement inhibitory factor'. A. fumigatus can bind specifically to different host tissues components, whereas toxins give a general and significant immunosuppressive effect on host defences. Circumstantial evidence links the production of elastinolytic proteases with the ability to cause disease. However, none of the reports demonstrates conclusively a decisive role for any of the virulence factors described thus far. It is conceivable that proteolytic enzyme activities such as those expressed by AFAlp are one of a number of factors, each with a minor effect, that combine to facilitate disease progression

Inflammatory cells and airway defense against Aspergillus fumigatus

The authors offer a summary of the attack strategies of A. fumigatus and interactions with the airway defense system. The possible role of proteolytic enzymes from Aspergillus in the inflammatory response of the airways is also discussed. Evidence is given for the in vivo production of these proteolytic enzymes in patients with ABPA and aspergilloma. The authors also describe the role of epithelial attack by proteolytic enzymes, the induction of a first wave of chemokines, the succeeding Th2-type inflammatory response in atopic patients, and the role of eosinophils in the continuation of this inflammatory cycle. Possibilities for inhibition of this continuous cycle of inflammation, followed by the resolution of ABPA. are discussed

Proteases from Aspergillus fumigatus induce release of proinflammatory cytokines and cell detachment in airway epithelial cell lines

Aspergillus fumigatus is a pathogen causing; diverse respiratory disorders, Several studies have suggested that fungal proteases may play a role in the pathogenicity of fungi, Since the airways are the most common route for entry of. A, fumigatus, this study focused on the ability of fungal proteases to induce the release of proinflammatory cytokines and to cause cell detachment in human pulmonary epithelial cell Lines. It was shown that fungal serine protease activity induced the production of interleukin (IL)-8 and IL-6 and monocyte chemotactic protein-1 and caused cell detachment in a dose-dependent fashion. Chymostatin, antipain, phenylmethylsulfonyl fluoride, and heat treatment completely inhibited fungal protease activity, cytokine production and cell detachment; antileukoprotease partially inhibited these activities. By causing cell detachment, fungal proteases may decrease the physical barrier function of the epithelium, however, by eliciting a cytokine response, the epithelium may signal the mucosal inflammatory response against A, fumigatus

Pulmonary aspergillosis

Aspergillus species are ubiquitous in the environment and are inevitably inhaled into the airways. Inhalation of Aspergillus conidia or mycelium fragments may result in colonisation of the airways. In susceptible hosts colonisation may subsequently cause disease. Patients with pre-existent cavities may develop aspergillomas which may be quiescent or cause symptoms especially recurrent haemoptysis. Acute invasive disease is potentially lethal in patients who are vulnerable to infection due to underlying lung diseases or immunosuppression. In addition to its ability to colonise the human respiratory tract. Aspergillus has a significant potential to act as a powerful allergen resulting in Aspergillus asthma and allergic bronchopulmonary aspergillosis. The various presentations of pulmonary disease caused by Aspergillus are reviewed here, focusing primarily on clinical aspects rather than basic science. (C) 2001 Elsevier Science BY. Ali rights reserved

Secretory leukoprotease inhibitor:a native antimicrobial protein presenting a new therapeutic option?

Secretory leukoprotease inhibitor (SLPI) is a low molecular weight serine protease inhibitor found on various mucosal surfaces and has been ascribed an important role in maintaining the protease-antiprotease balance of the airways. Recent scientific evidence has suggested that SLPI may also have a broad spectrum antibiotic activity that includes antiretroviral, bactericidal, and antifungal activity. Given the unpropitious development of drug resistance to infectious micro-organisms in the human population, the need for therapeutic alternatives in the treatment of infectious diseases has become clear. SLPI may prove valuable in the prophylaxis and future treatment of infectious diseases, yet the clinical efficacy of SLPI remains largely to be elucidated.</p