Mucosal leishmaniasis (ML), a severe chronic disease caused by le

Mucosal leishmaniasis (ML), a severe chronic disease caused by leishmania protozoa, remains a serious health problem in several parts of the world, including Brazil 1. ML is at the hyper-responsive end of the spectrum of clinical diseases caused by Leishmania braziliensis1. Uncontrolled immune responses have been implicated in ML pathogenesis because T lymphocytes from ML patients initiate intense responses (characterised by lymphoproliferation

and cytokine production) despite the low number of parasites in mucosal lesions 2–4. In addition to Th1 cytokines, TGF-β and IL-6 are also produced in ML lesions, but the significance of this finding is poorly understood 5. Th17 cells participate RO4929097 solubility dmso in

inflammatory responses to several human infectious agents 6, 7. IL-17, the Th17 signature cytokine, induces tissue damage mediated by neutrophil attraction and proteinase release. Neutrophil recruitment mediated by IL-17+ cells contributes to disease progression in susceptible mouse strains infected with L. major8. Although the cytokine combination that leads to human Th17 differentiation and maintenance remains controversial, TGF-β and IL-6, along with IL-23 and IL-1β, have been implicated in this phenomenon 9, 10. Recently in human ML, IL-17 expression has been detected 11, but the cell source of this expression has not yet been determined. In this study, we expand on the observations reported by Bacellar et al. 11 by demonstrating that in addition to Th17 cells, CD8+ and CD14+ cells express IL-17. We also this website detected the presence of neutrophils expressing proteinases in tissue-damaged areas, suggesting a potential function for Th17 cells in ML lesions. IL-17 expression was consistently higher in ML lesions (n=12) than in normal mucosal samples

(n=4), as shown in Fig. 1A and B. Marked expression was detected in mononuclear cells, endothelial cells and perivascular fusiform cells. No reactivity was detected using an isotype control antibody (Fig. 1G). As for Atorvastatin cytokines involved in IL-17 production, ML lesions presented an intense expression of both TGF-β, which is found in mononuclear cell aggregates and in endothelial cells disseminated throughout the inflammatory infiltrate (Fig. 1C), and IL-1β, which is detected mainly in mononuclear cells near the ulcer in the inflammatory infiltrate (Fig. 1D). IL-23 was heterogeneously distributed in ML patients, alternating between intense signals in mononuclear cells in some tissue samples (Fig. 1E) and only slight reactivity in other specimens. Weak IL-6 staining was occasionally observed in mononuclear cells located at periglandular areas and in blood vessels dispersed in the inflammatory infiltrate (Fig. 1F). Cytokine quantification analyses revealed higher expression of all cytokines in ML lesions than in normal mucosal tissue samples (Fig. 1H).

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