Host defense mechanisms against Candida auris

ABSTRACTIntroduction Candida auris is a pathogen of growing public health concern given its rapid spread across the globe, its propensity for long-term skin colonization and healthcare-related outbreaks, its resistance to a variety of antifungal medications, and the high morbidity and mortality associated with invasive disease. Despite that, the host immune response mechanisms that operate during C. auris skin colonization and invasive infection remains poorly understood.Areas covered In this manuscript, we review the available literature in the growing research field pertaining to C. auris host defenses and we discuss what is known about the ability of C. auris to thrive on mammalian skin, the role of lymphoid cell-mediated, IL-17-dependent defenses in controlling cutaneous colonization, and the contribution of myeloid phagocytes in curtailing systemic infection.Expert opinion Understanding the mechanisms by which the host immune system responds to and controls colonization and infection with C. auris and developing a deeper knowledge of tissue-specific host-C. auris interactions and of C. auris immune-evading mechanisms may help devise improved strategies for decolonization, prognostication, prevention, vaccination, and/or directed antifungal treatment in vulnerable patient populations.KEYWORDS: Candida aurisyeastfungal infectionIL-17phagocytesemerging pathogenskin colonization Article highlights Candida auris is a pathogen of growing public health concern given its propensity to persistently colonize the human skin and environmental surfaces and thereby cause outbreaks in healthcare settings, as well as due to the high prevalence of resistance to conventional antifungal agents.C. auris grows avidly in human sweat conditions where it forms multilayer, complex biofilms. Concordantly, effective C. auris skin colonization has been demonstrated in a porcine and human skin models ex vivo and in a mouse model of epicutaneous application in vivo.IL-17A and IL-17F production by innate and adaptive lymphoid cells is critical for curtailing C. auris skin colonization and accelerating fungal clearance in the skin. Yet, despite the induction of potent protective local IL-17 responses, C. auris can persist long-term on the murine skin surface and in deeper skin tissue compartments including hair follicles, potentially concealing its detection by routine clinical surveillance and diagnostic methods.C. auris exhibits a unique mannan structure relative to C. albicans. This mannan structure a) may underlie the dependence on different C-type lectin receptors (i.e., complement receptor 3 and mannose receptor versus Dectin-1) for C. auris recognition and pro-inflammatory cytokine production by mononuclear phagocytes relative to C. albicans and b) may enable its evasion from neutrophil antifungal effector functions such as fungal uptake, killing, and extracellular trap formation.Different strains from various C. auris geographic clades seem to elicit highly variable transcriptional and antifungal effector activities in monocytes/macrophages. Comparative evaluation of a large collection of C. auris strains will be needed to precisely define the stain-dependent differences in mounting innate immune responses by phagocyte subsets. • Hyr1p-targeted and Als3-based strategies decrease tissue fungal burden and mortality of C. auris-infected mice in the animal model of hematogenous disseminated candidiasis. These findings show promise for the eventual development of preventive and/or therapeutic interventions in vulnerable patients.Declaration of interestsThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Author contributionsAll authors substantially contributed to the conception and design of this review article and interpreting the relevant literature and were involved in writing and/or revising the article for intellectual content.Additional informationFundingThis paper was funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (ZIA AI001175)