Background: The innate immune response to microbial pathogens can protect the host after a pathogen contact. This response is primarily mediated by macrophages and PMNs. Variable expression of Toll-like receptors (TLR) on the surface of human PMNs has been reported. TLR2, 4 and 9 are involved in host defences against C. albicans and A. fumigatus. The main goal of this study was to investigate the influence of Caspofungin (CSP), C. albicans and A. fumigatus on the expression of TLR2, 4 and 9. Methods: PMNs were isolated from healthy donors. PMNs, C. albicans and A. fumigatus were adjusted to 2x10^7. The pathogens were incubated in six-well plates at different concentrations of CSP for 2h. After incubation, PMNs were added and incubated for 30min. The RNA was isolated, cDNA was synthesized and Real-Time PCR was performed. RNA from ten healthy donors in the Candida group and from nine donors in the Aspergillus group was pooled. Expression of TLR2, 4 and 9 of PMNs was determined. Results: TLR9 expression was increased in comparison to TLR2 and 4. TLR9 was 2- fold upregulated in presence of A. fumigatus and 4-fold upregulated in the presence of A. fumigatus and CSP (0.05Âµg/ml) in comparison to the PMN control. Expression of TLR2 and 4 was not altered. For C. albicans, a 4-fold downregulation of TLR9 was observed. An upregulation in the presence of C. albicans and CSP (0.05Âµg/ml) was demonstrated. The highest expression of TLR9 in both groups was obtained at CSP (0.05 Âµg/ml). The other TLRs were not altered and did not demonstrate significant regulation. Conclusions: The present study demonstrated that TLRs, especially TLR9, play an important role in governing the function of PMNs in fungal infections and the associated inflammatory process. CSP and A. fumigatus can enhance the expression of TLR9, which seems to be relevant for the recognition of A. fumigatus and might therefore have an immunmodulatory effect with potential implications for antifungal treatment.
Full conference title:
46th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 46th