A number of diverse human pathogenic fungi produce proteases that can degrade immune proteins in the central nervous system
Abstract number: P822
Objectives: In invasive fungal infections, the high lethality rate of more than 90% in cases of the affection of the central nervous system (CNS) indicates an insufficiency of the local immunity. We studied the capacity of diverse pathogenic fungi to degrade components of the complement system and functional surface proteins of immune cells in the CNS.
Methods: Pathogenic species of Aspergillus, the Pseudallescheria/Scedosporium cluster and some members of Zygomycetes were grown in medium or cerebrospinal fluid (CSF), with or without supplements. Degradation of soluble complement proteins was evaluated by Western Blot. Hyphal opsonization was examined by immunofluorescence; cellular expression of surface proteins was quantified by FACS.
Results: The growth of Aspergillus spp in CSF resulted in secretion of proteolytic factors which degraded various complement proteins. The extent of the proteolysis was dependent on the time period of fungal growth and the Aspergillus species. A. fumigatus, the predominant cause of cerebral aspergillosis, induced a rather quick and strong degradation. The fungal secretion of proteases correlated with a diminished opsonization of Aspergillus hyphae by complement proteins and proteolytic destruction of complement receptor CR3 (CD11b/CD18) on the surface of immune cells. Both opsonization of pathogens and recognition of deposited complement proteins by receptors are crucial for an efficient antifungal attack.
Other Aspergillus species and further pathogenic fungi could also be shown to secrete proteolytic factors. Compared to environmental isolates, patient isolates of Aspergillus terreus seemed to destroy complement more rapid. Within the Pseudallescheria/Scedosporium cluster, the asexual form Scedosporium generally appears to be more active in this regard than the perfect stadium Pseudallescheria. Among Zygomycetes, we found complement-degrading isolates of Rhizomucor pusillus and Rhizopus microsporus. Candida spp. and Cryptococcus neoformans will be tested next.
Conclusions:Aspergillus spp and other pathogenic fungi secrete proteases which can efficiently degrade complement proteins. This may represent a pivotal evasion mechanism especially in the CNS that is separated from the peripheral immune weapons by the blood-brain-barrier. On the other hand, these proteases represent an interesting therapeutic target to decrease the lethality of cerebral fungal infections.
|Session name:||Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Vienna, Austria, 10 - 13 April 2010|
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