No abstract

Chronic mucocutaneous candidiasis constitutes a heterogeneous group of syndromes, characterized by non-invasive infection of the skin, nails and mucosal membranes by the fungus Candida spp. Although symptoms are heterogeneous, in all cases there is a reduction in protective cytokines, favouring the development of disease. The normal role of cytokines in skin lesions is not well understood. The present study aimed to investigate the progression of disease, understand specific cellular and molecular components involved in immunity to Candida albicans and determine the balance between pro-and anti-inflammatory cytokines over the course of cutaneous infection in immunocompetent mice. BALB/c mice (five per group) were inoculated with 5610 6 C. albicans pseudohyphae in the deep dermis of the paw and analysed over 1-14 days post-infection. The contralateral paws were used for negative controls. Haematoxylin and eosin staining of skin sections during C. albicans infection was performed to analyse structural modifications to the epidermis such as hyperplasia, and infiltration of neutrophils and fibroblasts in the dermis. The cytokine populations were determined by capture ELISA using popliteal lymph node tissue. Pro-inflammatory cytokines were detected at significant levels during the initial phase of cutaneous infection and correlated with the rapid elimination of C. albicans. Anti-inflammatory cytokines (IL-13, IL-4, IL-10 and transforming growth factor-b) were detected on day 4 post-infection, and prevented exacerbation of inflammation and participated in healing of lesions. Thus, a balance between pro-and anti-inflammatory cytokines was fundamental for the resolution of infection. Importantly, these findings broaden our understanding of the immune mechanisms involved in chronic cutaneous candidiasis. INTRODUCTIONCandida albicans is a commensal organism found on human skin and in mucous membranes, and causes candidiasis only if the normal host-pathogen balance is disrupted. Chronic mucocutaneous candidiasis is caused by the selective inability of a patient to clear a Candida infection, resulting in persistent debilitating inflammation of the skin, nails and mucous membranes (Kirkpatrick, 2001). A variety of clinical conditions that impair immune function, such as infection by human immunodeficiency virus or the use of corticosteroids, favour the development of chronic mucocutaneous candidiasis; the disease may also be associated with endocrinopathies or genetic defects in the immune system (Chehimi et al., 2001;Collins et al., 2006).A more critical parameter in the pathogenesis of chronic cutaneous candidiasis might be the cytokine secretion of T-cell subtypes. Numerous studies have described altered cytokine production with reduced production of type 1 cytokines, such as IFN-c, IL-12 and IL-2, and increased secretion of IL-10 or IL-4 and IL-5 (Kobrynski et al., 1996;Lilic et al., 2003;van der Graaf et al., 2003;Eyerich et al., 2007). In T-helper 1 (Th1) responses, IL-12 and IFN-c production are essential for contro...

These findings highlight some important changes in diabetic animal responses to C. albicans infection that may be important to the pathophysiological processes underpinning cutaneous candidiasis in diabetic patients.