,37 who demonstrated that thymosin-α1 stimulates the Th1-polarizing capacity of DC. CpG was also shown to
act as a potent adjuvant for the vaccine-induced protection against the fungus by promoting a dominant Th1 response to Aspergillus antigens and allergens.38,39 Given the capacity of CpG to stimulate the release of type I IFN by plasmacytoid DCs, it is tempting to speculate that these cytokines can act as immuno-adjuvants in fungal defence. In addition, the capacity of type I IFN to exert an anti-fungal activity by promoting natural killer cell activation in mice40,41 suggests that these cytokines could represent a promising adjuvant able to reinforce also the Rapamycin purchase innate defence mechanisms such as those involving natural killer cells. Based on these data, we investigated whether IFN-β could also modulate the T-cell polarizing capacity of A. fumigatus-stimulated DCs, which fail to secrete this cytokine when challenged with A. fumigatus conidia. Interestingly, we observed that the exogenous addition of IFN-β to A. fumigatus-stimulated
DCs reinforced the expression of CD86, CD83 and IL-12p70 and, in turn, the capacity to stimulate a Th1 response. Moreover, in the presence of IFN-β, DCs may also express IL-27, a key cytokine involved in controlling excessive inflammation by suppressing Th17 differentiation.42 In addition to that, in this scenario IFN-β could MK-2206 in vitro also limit the development of a Th17 inflammatory response acting directly on T cells as recently proposed in patients with multiple sclerosis undergoing IFN-β therapy.43,44 Collectively these data identified a novel effect of IFN-β on the anti-Aspergillus immune response which, in turn, might open new perspectives on the use of IFN-β as a candidate adjuvant in immunotherapy for fungal infections aimed at potentiating DC immunological functions. We would like to thank Eugenio Morassi for preparing the drawings and
Pierre-Emmanuel CYTH4 Colle and Claudine Pinel for invaluable discussions. This work was supported by an Italian Public Health Ministry grant (Ricerca Finalizzata 2006; #8ABF). The authors declare no conflict of interest. “
“Epithelial cells act as the first line of host defense against microorganisms by producing a range of molecules for clearance. Proinflammatory cytokines facilitate the clearance of invaders by the recruitment and activation of leukocytes. Upregulation of cytokine expression thus represents an important host innate defense response against invading microorganisms such as Streptococcus pneumoniae. Histological analysis of the airway revealed less leukocyte infiltration during the early stage of pneumococcal infection, when compared with nontypable Haemophilus influenzae (NTHi) infection. Here, we report that S. pneumoniae is less potent in inducing proinflammatory cytokine expression compared with NTHi. Among numerous virulence factors, pneumococcal pneumolysin was found to be the major factor responsible for the induction of inflammation.