Toll-Like Receptor 2 is the Major Cytokine Signalling Receptor for Aspergillus fumigatus

Bart-Jan Kullberg, Adilia Warris, Paul E. Verweij, Mihai G. Netea

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Background: Invasive aspergillosis is an important cause of mortality in immunocompromized host. It has recently been suggested that Toll-like receptor (TLR)-4 is involved in the intracellular signalling for NFkB translocation by Aspergillus, without leading to production of Tumor Necrosis Factor alpha (TNF). Methods: We investigated the role of TLR 2 and 4 in the signalling for proinflammatory cytokine production by Aspergillus hyphae or conidia. Results: When freshly isolated human PBMC were stimulated for 24h in vitro with 107 heat-killed A. fumigatus conidia, significant amounts of TNF and IL-1b were produced. Stimulation with hyphae led to a 5 to 10-fold higher cytokine induction (p<.05 addition="" of="" serum="" resulted="" in="" to="" further="" increase="" a="" monoclonal="" anti-tlr2="" antibody="" blocked="" tnf="" induction="" by="" hyphae="" vs.="" ng="" p="" or="" conidia="" contrast="" anti-tlr4="" had="" only="" marginal="" effects="" on="" either="" conidia.="" similar="" blocking="" tlr4="" but="" not="" tlr2="" were="" obtained="" for="" il-1="" production.="" conclusions:="" aspergillus="" cell="" wall="" components="" stimulate="" cytokine="" production="" serum-dependent="" manner.="" this="" stimulation="" is="" mediated="" through="" whereas="" marginally="" involved.="">

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    • ICAAC 42nd