IL-17 (IL-17A) has emerged as an integral mediator of protection against extracellular microbes but this cytokine also drives pathology in various autoimmune diseases. forms. For these species dimorphism is usually a key feature of virulence and the tissue-invasive hyphal form is generally the most pathogenic (5). The recognition of different morphotypes by the host permits discrimination between commensal and pathogenic disease-causing forms of (6-9) (see section 2 below). 1 Mucocutaneous Candidiasis There are multiple manifestations of candidiasis differing in the immune response invoked. Mucocutaneous candidiasis encompasses infections from the mucosae nail and skin materials broadly. infections in the mouth is certainly termed oropharyngeal candidiasis (OPC) or thrush and it is often minor and self-limiting. OPC is among the first clinical symptoms of HIV and OPC is certainly common in neonates older people sufferers with xerostomia (dry-mouth) and people going through chemotherapy and radiotherapy for head-neck malignancies. Severe situations in infants can result in malnutrition and a failure to thrive. OPC is also a risk factor for esophageal cancer (10). Chronic mucocutaneous candidiasis (CMC) presents as OPC and superficial lesions around the mucosa or AEB071 thickened skin and nails and is typically refractory to treatment. CMC occurs in patients with underlying genetic defects in IL-17-related immunity (10 11 Although not life threatening significant morbidity is usually associated with OPC and CMC due to pain weight loss and decreased nutritional intake. 1 Vaginal Candidiasis colonizes the reproductive tract in most women without pathological consequence but at least one episode of vulvovaginal E.coli monoclonal to V5 Tag.Posi Tag is a 45 kDa recombinant protein expressed in E.coli. It contains five different Tags as shown in the figure. It is bacterial lysate supplied in reducing SDS-PAGE loading buffer. It is intended for use as a positive control in western blot experiments. candidiasis (VVC) is usually diagnosed in 75% of women of reproductive age (12). Recurrent VVC though infrequent AEB071 is usually associated with significant treatment costs and decreased quality of life. Consequently experimental vaccines against are being evaluated in the context of chronic VVC (13 14 1 Disseminated Candidiasis Systemic candidiasis is the most severe form of contamination. species represent the fourth most common cause of bloodstream infections in U.S. hospitals with a mortality rate of 40-60% (10). Systemic candidiasis is typically caused by medical intervention including indwelling catheters antibiotics or abdominal medical procedures. Notably mucocutaneous overgrowth of is not usually associated with invasive disease indicating tissue-specific compartmentalization of responses to (15 16 1 Candida in the intestinal tract Although does not usually invade intestinal tissue to cause disease species colonize the GI tract and can translocate to the bloodstream during intestinal barrier breaches (10 17 While GI translocation of into circulation is AEB071 not common systemic invasion resulting from damage to the GI tract as during abdominal surgery is usually a significant problem (18). As will be described throughout this review there are numerous immune mechanisms that participate in anti-immunity the dominance of which varies among tissues. Oral and dermal candidiasis are strongly IL-17-dependent whereas immunity to vaginal candidiasis relies more on extrinsic factors such as microbial flora and changes in pH (14 19 Although systemic candidiasis has an IL-17 component IFNγ from Th1 and NK cells seems to play a relatively more important role (1 20 AEB071 Studies using an intragastric colonization model indicated that Th1 cells and IL-22 were the dominant protective factors whereas Th17 cells and IL-17 promote tissue destruction in this setting (21 22 Murine models of disseminated OPC vaginal and cutaneous candidiasis are established that recapitulate human candidiasis with affordable fidelity (23-26) and thus offer a cost-effective platform to study the immune response to and to facilitate development of new therapeutics. 2 Pattern Recognition of Candida albicans Although excellent reviews of the pattern recognition receptors (PRRs) involved in recognition of are available (27-29) a brief discussion of this topic is usually in order. C-type lectin receptors (CLRs) particularly Dectin-1 are the main sensors of species although there’s also significant efforts from TLRs and Nod-like receptors. The cell wall structure includes an external mannoprotein level that conceals an internal layer made up of β-glucan derivatives and chitin. CLRs recognize carbohydrate moieties within the fungal cell wall structure including mannans (Dectin-2 ?3 Mincle the mannose receptor amongst others) chitin (receptor unidentified) and ??glucan (Dectin-1). Activation of.