Complement induction and complement evasion in patients with cerebral aspergillosis.
Cerebral aspergillosis is a mostly lethal infection of the central nervous system. Former results identified low cerebral complement levels as one cause for insufficient immune reaction. Therefore we studied cerebral complement expression after fungal invasion and investigated putative mechanisms of Aspergillus spp to cope with the complement-induced selection pressure. Brain tissue derived from patients with cerebral aspergillosis or non-infected individuals was analyzed immunohistochemically for complement synthesis. Correlations between expression levels were determined statistically. Increased complement synthesis, a prerequisite for strengthened antifungal potency, was visible in resident astrocytes, neurons, oligodendrocytes as well as in infiltrating macrophages after fungal infection. Surprisingly, microglia, although regarded as major immune cells, only marginally participated in synthesis of most complement proteins. Several evasion mechanisms were found that help the fungus to establish a cerebral infection even in the presence of complement: Fungal hyphae limit the surface deposition of C3 and thus interfere with complement-dependent phagocytosis. Furthermore, the "sealing off" in brain abscesses not only inhibits fungal spreading but also forms protection shields against complement attack. Complement indeed seems to represent an important selection pressure and evokes the development of fungal evasion mechanisms. Counteractions for these evasion processes might represent interesting therapeutic approaches.
Rambach
Günter
G
Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, Fritz-Pregl-Str. 3, 6020 Innsbruck, Austria.
Maier
Hans
H
Vago
Gianluca
G
Mohsenipour
Iradj
I
Lass-Flörl
Cornelia
C
Defant
Alexandra
A
Würzner
Reinhard
R
Dierich
Manfred P
MP
Speth
Cornelia
C
D000328:Adult; D000368:Aged; D001230:Aspergillus / Q000276:immunology*; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000276:immunology* / Q000382:microbiology*; D003165:Complement System Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020953:Neuroaspergillosis / Q000276:immunology*
D003165:Complement System Proteins