RESUMO
PURPOSE: Diabetic patients seem to be predisposed to cutaneous candidiasis. In this study, we evaluated the interference of diabetic conditions in alloxan-induced diabetic mice in relation to the development of C. albicans infection, density of M1 and M2 macrophages, distribution of collagen type I and III and anti-inflamamatory cytokines involved in tissue repair. METHODOLOGY: The mice were treated with intravenous alloxan, and all animals with blood glucose levels >250 mg dl-1 were inoculate with C. albicans intradermally in the hind paw and were studied for up to 21 days. Control groups without alloxan were used. The fungal burden was evaluated by periodic acid-Schiff (PAS) and by counting the colony forming units. Total population of macrophages were targeted with antibody to F4/80 antigen and M2 macrophages with anti-arginase antibody. Anti-inflammatory cytokines from popliteal lymph nodes were determined by capture ELISA procedures. Picrosirius red staining allowed qunantification of collagen types I and III in the infected skin by using a polarized light microscope.Results/Key findings. Diabetic mice, versus non-diabetic mice, showed a significant lower density of F4/80 and M2 macrophages, higher fungal burden, deficiency in interleukin (IL)-4 production, and delayed IL-13 responses. The later clearance of C. albicans enhanced tissue injury, leading to a decrease in collagen type I. Moreover, collagen type III was increased by interference of IL-13 and transforming growth factor-ß cytokines. CONCLUSION: 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.
Assuntos
Candidíase Cutânea/microbiologia , Candidíase Cutânea/fisiopatologia , Diabetes Mellitus Experimental/complicações , Cicatrização , Animais , Glicemia/análise , Candida albicans/crescimento & desenvolvimento , Candida albicans/imunologia , Candida albicans/fisiologia , Candidíase Cutânea/etiologia , Candidíase Cutânea/imunologia , Colágeno/análise , Citocinas/análise , Citocinas/imunologia , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/fisiopatologia , Modelos Animais de Doenças , Interleucina-13/análise , Interleucina-4/análise , Macrófagos/imunologia , Masculino , Camundongos , Pele/químicaRESUMO
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 5 × 10(6)C. albicans pseudohyphae in the deep dermis of the paw and analysed over 1-14â 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 (IL-6, TNF-α, IL-12, IFN-γ and IL-17) 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-ß) 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.
Assuntos
Candida albicans/crescimento & desenvolvimento , Candida albicans/imunologia , Candidíase Cutânea/imunologia , Candidíase Cutânea/patologia , Pele/imunologia , Pele/patologia , Animais , Citocinas/análise , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Histocitoquímica , Linfonodos/imunologia , Camundongos Endogâmicos BALB C , Microscopia , Neutrófilos/imunologiaRESUMO
Antibody titers against Candida albicans and Pityrosporum orbiculare, the presumed etiologic agent of tinea versicolor, were determined in normal subjects, and in patients with tinea versicolor or chronic mucocutaneous candidiasis. Whereas antibody against both organisms was found in low titer in normal subjects, a majority of patients with each infection had elevated antibody titers against the infecting organism. Patients infected with one organism did not have elevated titers against the other, and titers against one did not correlate with titers against the other. Therefore, these studies indicate that both of the superficial infections are capable of inducing a significant humoral immune response and that actual infection with the organism rather than mere colonization is required for production of the elevated antibody titers.