Mucosal leishmaniasis: in situ characterization of the host inflammatory response, before and after treatment

Amato, Valdir Sabbaga; Andrade, Heitor Franco de; Duarte, Maria Irma Seixas

doi:10.1016/s0001-706x(02)00260-7

Cited by 52 publications

(62 citation statements)

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“…Flow cytometric analysis revealed that about 3% of mucosal lesion cells express either IFN-g or IL-17, but less than 0.5% co-express IFN-g and IL-17 (data not shown). In addition to the previously described roles of Th1 clones and the critical effector cytokine IFN-g in ML pathogenesis [5], these cells are involved in Th17 recruitment to tissue lesions. For example, the recruitment of Th17 cells is stimulated by a Th1 clone in psoriatic lesions [13].…”

Section: Resultsmentioning

confidence: 94%

“…2F) and CD14 1 (Fig. 2I) [4][5][6][7][8][9][10][11][12][13][14][15][16]. The local detection of CD8 1 IL-17 1 cells is of particular interest since a noncytotoxic 17 (Tc17) CD27 1/À CD28 1 CD45RA À subset has recently been described in other inflammatory diseases [17].…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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Human mucosal leishmaniasis: Neutrophils infiltrate areas of tissue damage that express high levels of Th17‐related cytokines

et al. 2010

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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...

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Human mucosal leishmaniasis: Neutrophils infiltrate areas of tissue damage that express high levels of Th17‐related cytokines

et al. 2010

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“…Sendo assim, os achados de IgE antiLeishmania no presente estudo, podem estar associados aos processos iniciais da evolução da doença e consequentemente, ao perfil TH2 de resposta imune nesses pacientes. Por outro lado, em leishmaniose mucosa há uma mistura de perfil de resposta TH1 e TH2, antes e após tratamento 1 .…”

Section: Discussionunclassified

Perfil de isotipos de imunoglobulinas e subclasses de IgG na leishmaniose tegumentar americana

Souza

Afonso-Cardoso

et al. 2005

Rev. Soc. Bras. Med. Trop.

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RESUMOParasitas do gênero Leishmania são protozoários intracelulares obrigatórios que causam um complexo de enfermidades no homem e animais denominadas leishmanioses. Essas infecções atingem cerca de 12 milhões de pessoas em todo o mundo e são consideradas uma das dez principais doenças tropicais pela Organização Mundial da Saúde 27 . De acordo com este órgão, a forma tegumentar dessa parasitose é a apresentação clínica mais comum, acometendo cerca de 75% dos casos e constituindo um grave problema de saúde pública. A importância dessa moléstia não se deve apenas à sua alta incidência e ampla

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Association between skin parasitism and a granulomatous inflammatory pattern in canine visceral leishmaniosis

dos-Santos

David

Badaró

et al. 2004

Parasitology Research

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In this work we examined 76 stray dogs from an area of endemic visceral leishmaniosis, in order to determine whether the presence of skin inflammation or a specific inflammatory pattern could be taken as indicative of infection with Leishmania chagasi, and whether the parasite burden in the skin could be associated with the intensity or the nature of the inflammatory process. Inflammatory infiltrates were observed in the skin of 51 out of 55 animals with diagnosis of leishmaniosis, and in 17 out of 21 animals without signs of infection. Amastigotes were identified in the skin of 29 out of the 55 animals with diagnosis of leishmaniosis. Granuloma and a monomorphic macrophage inflammatory infiltrate, and not a mixed focal or mixed diffuse inflammation, were significantly associated with skin parasitism, both in terms of frequency ( P=0.015 in the Chi-square test) and intensity ( P=0.005 in the Kruskal-Wallis test). A low parasite burden was associated with a multifocal inflammatory pattern.

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Mucosal leishmaniasis: in situ characterization of the host inflammatory response, before and after treatment

Cited by 52 publications

References 31 publications

Human mucosal leishmaniasis: Neutrophils infiltrate areas of tissue damage that express high levels of Th17‐related cytokines

Human mucosal leishmaniasis: Neutrophils infiltrate areas of tissue damage that express high levels of Th17‐related cytokines

Perfil de isotipos de imunoglobulinas e subclasses de IgG na leishmaniose tegumentar americana

Association between skin parasitism and a granulomatous inflammatory pattern in canine visceral leishmaniosis

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