Candidaand Complement: New Aspects in an Old Battle

Candidais a dominant fungal pathogen in immunocompromised hosts, leading to opportunistic infections. Complement with its multifaceted functions is involved in the immune defense against this yeast, and recently several novel aspects have emerged in this old battle. It is clear thatCandidacan adopt both roles as a colonizer or as a pathogen. In our article, we focus on the molecular mechanisms of theCandida-complement interplay, which occur in disseminated disease as well as locally on skin or on mucous membranes in mouth and vagina; the mechanisms can be supposed to be the same. Activation of the complement system byCandidais facilitated by directly triggering the three dominant pathways, but also indirectly via the coagulation and fibrinolysis systems. The complement-mediated anti-Candidaeffects induced thereby clearly extend chemotaxis, opsonization, and phagocytosis, and even the membrane attack complex formed on the fungal surface plays a modulatory role, although lysis of the yeastper secannot be induced due to the thick fungal cell wall. In order to avoid the hostile action of complement, several evasion mechanisms have evolved during co-evolution, comprising the avoidance of recognition, and destruction. The latter comes in many flavors, in particular the cleavage of complement proteins by yeast enzymes and the exploitation of regulatory proteins by recruiting them on the cell wall, such as factor H. The rationale behind that is that the fluid phase regulators on the fungal cell surface down-regulate complement locally. Interestingly, however, evasion protein knockout strains do not necessarily lead to an attenuated disease, so it is likely more complexin vivothan initially thought. The interactions between complement and non-albicansspecies also deserve attention, especiallyCandida auris, a recently identified drug-resistant species of medical importance. This is in particular worth investigating, as deciphering of these interactions may lead to alternative anti-fungal therapies directly targeting the molecular mechanisms.