Modulation of monocyte and B cell functions by humoral immunity in response to Candida albicans

Protection from C. albicans infection is mainly based on innate cellular immunity that is fine-tuned by T cells. Project C4 aims at elucidating how C. albicans changes the humoral immune response to affect the cellular response, Monocytes/macrophages are an essential part of antifungal immunity, in part due to their regulatory role at the intersection of innate and adaptive immune responses. In the first funding period we characterized the reaction of monocytes to C. albicans and found that monocytes release extracellular DNA nets (ETs) that trap the fungal cells in a manner similar to neutrophilic granulocytes. These ETs contain substances like citrullinated histones and myeolperoxidase that attack the fungus. C. albicans is known to recruit human regulators like complement factor H to the surface to inhibit innate immune reactions like complement activation and opsonization. Recently we identified kallikrein, which is activated from prekallikrein in response to contact activation on the C. albicans surface as a complement activator that cleaves C3 and factor B. However, factor H on C. albicans also inhibits this pathway of complement activation. Further studies will include the detailed analysis of fungal proteins and recruited human complement regulatory proteins (FHR1) and their interaction with monocytes and B cells via distinct receptors. Furthermore, the analysis of B cell populations reacting to C. albicans in reporter mice infected or colonized with C. albicans will give insights into the in vivo immune response to C. albicans.