Aspergillus fumigatus cell wall components differentially modulate host TLR2 and TLR4 responses.
Aspergillus fumigatus conidia attenuates host proinflammatory responses through modulation of Toll-like receptor (TLR)2 and TLR4 signaling, but the precise mechanisms that mediate this effect are not known. In the present study, the role of the Aspergillus cell wall polysaccharide constituents responsible for the modulation of host capability to mount a proinflammatory response was studied. Aspergillus cell wall fractions and its major components showed differential capabilities in modulating host TLR-mediated interleukin (IL)-6 production. Beta-glucan specifically suppressed TLR4-induced response, while alpha-glucan inhibited IL-6 induced through TLR2- and TLR4-stimulation. Galactomannan diminished TLR4-mediated response, while its inhibitory effects on TLR2-signaling were limited. Chitin, on the other hand, did not have significant immunomodulatory capability. The ability of the fungal cell wall to alter the immune signature of the pathogen may contribute to its virulence and the pathogenesis of co-infection.
Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Louis Y A
LY
Chai
Alieke G
AG
Vonk
Bart Jan
BJ
Kullberg
Paul E
PE
Verweij
Ineke
I
Verschueren
Jos W M
JW
van der Meer
Leo A B
LA
Joosten
Jean-Paul
JP
Latgé
Mihai G
MG
Netea
D000818:Animals; D001228:Aspergillosis / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism*; D002457:Cell Extracts / Q000276:immunology; D002473:Cell Wall / Q000737:chemistry* / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000276:immunology; D011134:Polysaccharides / Q000276:immunology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D000099181:Dectin-1
D002457:Cell Extracts; D016207:Cytokines; D015850:Interleukin-6; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011134:Polysaccharides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D000099181:Dectin-1