Mucosal leishmaniasis (ML) is characterised by severe tissue destruction. Herein, we evaluated the involvement of the IL-17-type response in the inflammatory infiltrate of biopsy specimens from 17 ML patients. IL-17 and IL-17-inducing cytokines (IL-1b, IL-23, IL-6 and TGF-b) were detected by immunohistochemistry in ML patients. IL-17 1 cells exhibited CD4 1 , CD8 1 or CD14 1 phenotypes, and numerous IL-17 1 cells co-expressed the CC chemokine receptor 6 (CCR6). Neutrophils, a hallmark of Th17-mediated inflammation, were regularly detected in necrotic and perinecrotic areas and stained positive for neutrophil elastase, myeloperoxidase and MMP-9. Taken together, these observations demonstrate the existence of Th17 cells in ML lesions associated with neutrophils in areas of tissue injury and suggest that IL-17 is involved in ML pathogenesis.Key words: Human . Mucosal leishmaniasis . Neutrophils . Th17 IntroductionMucosal 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 hyperresponsive end of the spectrum of clinical diseases caused by Leishmania braziliensis [1]. 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][3][4]. In addition to Th1 cytokines, TGF-b and IL-6 are also produced in ML lesions, but the significance of this finding is poorly understood [5].Th17 cells participate 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 1 cells contributes to disease progression in susceptible mouse strains infected with L. major [8]. Although the cytokine combination that leads to human Th17 differentiation and maintenance remains controversial, TGF-b and IL-6, along with IL-23 and IL-1b, have been implicated in this phenomenon [9,10].Recently in human ML, IL-17 expression has been detected determined. In this study, we expand on the observations reported by Bacellar et al. [11] by demonstrating that in addition to Th17 cells, CD8 1 and CD14 1 cells express IL-17. We also detected the presence of neutrophils expressing proteinases in tissue-damaged areas, suggesting a potential function for Th17 cells in ML lesions. Results and discussionExpression of IL-17, Th17-inducing cytokines and retinoic acid-related orphan receptor ct (RORrt) IL-17 expression was consistently higher in ML lesions (n 5 12) than in normal mucosal samples (n 5 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 cytokines involved in IL-17 production, ML lesions presented an intense expressio...

The cell wall has a critical role in the host immune response to fungal pathogens. In this study, we investigated the influence of two cell wall fractions of the dimorphic fungi Paracoccidioides brasiliensis (Pb) in the in vitro generation of monocyte-derived dendritic cells (MoDCs). Monocytes were purified from the peripheral blood of healthy donors and cultivated for 7 days in medium supplemented with IL-4 and GM-CSF in the presence of Pb cell wall fractions: the alkali-insoluble F1, constituted by β-1,3-glucans, chitin and proteins, and the alkali-soluble F2, mainly constituted by α-glucan. MoDCs phenotypes were evaluated regarding cell surface expression of CD1a, DC-SIGN, HLA-DR, CD80, and CD83 and production of cytokines. The α-glucan-rich cell wall fraction downregulated the differentiation of CD1a+ MoDCs, a dendritic cell subset that stimulate Th1 responses. The presence of both cell fractions inhibited DC-SIGN and HLA-DR expression, while the expression of maturation markers was differentially induced in CD1a– MoDCs. Differentiation upon F1 and F2 stimulation induced mixed profile of inflammatory cytokines. Altogether, these data demonstrate that Pb cell wall fractions differentially induce a dysregulation in DCs differentiation. Moreover, our results suggest that cell wall α-glucan promote the differentiation of CD1a– DCs, potentially favoring Th2 polarization and contributing to pathogen persistence.

Aim Oral mucositis is a debilitating side‐effect of conventional cancer treatment, particularly of the head and neck region. This review aimed to evaluate existing evidence to identify optimal nutritional interventions for oral mucositis management in adult populations receiving treatment for cancer. Methods CINAHL, PubMed, Embase and Scopus were searched from database inception to July 2019, with each eligible article critically appraised for risk of bias and assigned a quality rating. Certainty of evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation system. Results Twenty‐three articles were identified (total unique study participants n = 7605). Nine intervention areas were identified. Certainty of evidence was moderate for oral cryotherapy in patients with solid or haematological cancers receiving 5‐Fluorouracil or high‐dose Melphalan chemotherapy prior to haematopoietic stem cell transplantation; and low for zinc supplementation for patients with oral cancer undergoing radiotherapy or chemoradiotherapy. Moderate certainty of evidence exists to recommend against glutamine supplementation in all cancer patients. Conclusion Research must determine the safety and efficacy of identified interventions to guide clinical practice. Addressing limitations requires larger, higher‐quality trials to increase evidence certainty.