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1.
PLoS Negl Trop Dis ; 16(1): e0010162, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35089930

RESUMO

American Tegumentary Leishmaniasis (ATL) is an endemic and neglected disease of South America. Here, mucosal leishmaniasis (ML) disproportionately affects up to 20% of subjects with current or previous localised cutaneous leishmaniasis (LCL). Preclinical and clinical reports have implicated the Leishmania RNA virus-1 (LRV1) as a possible determinant of progression to ML and other severe manifestations such as extensive cutaneous and mucosal disease and treatment failure and relapse. However, these associations were not consistently found in other observational studies and are exclusively based on cross-sectional designs. In the present study, 56 subjects with confirmed ATL were assessed and followed out for 24-months post-treatment. Lesion biopsy specimens were processed for molecular detection and quantification of Leishmania parasites, species identification, and LRV1 detection. Among individuals presenting LRV1 positive lesions, 40% harboured metastatic phenotypes; comparatively 58.1% of patients with LRV1 negative lesions harboured metastatic phenotypes (p = 0.299). We found treatment failure (p = 0.575) and frequency of severe metastatic phenotypes (p = 0.667) to be similarly independent of the LRV1. Parasite loads did not differ according to the LRV1 status (p = 0.330), nor did Leishmanin skin induration size (p = 0.907) or histopathologic patterns (p = 0.780). This study did not find clinical, parasitological, or immunological evidence supporting the hypothesis that LRV1 is a significant determinant of the pathobiology of ATL.


Assuntos
Leishmania/patogenicidade , Leishmania/virologia , Leishmaniose Cutânea/parasitologia , Leishmaniavirus/isolamento & purificação , Adulto , Estudos de Coortes , Humanos , Leishmania/classificação , Leishmaniose Cutânea/patologia , Leishmaniose Mucocutânea/parasitologia , Leishmaniose Mucocutânea/patologia , Leishmaniavirus/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Falha de Tratamento
2.
J Pathol ; 243(3): 320-330, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28799208

RESUMO

Monocytes infiltrating scar tissue are predominantly viewed as progenitor cells. Here, we show that tissue CCR2+ monocytes have specific immunosuppressive and profibrotic functions. CCR2+ monocytic cells are acutely recruited to the lung before the onset of silica-induced fibrosis in mice. These tissue monocytes are defined as monocytic myeloid-derived suppressor cells (M-MDSCs) because they significantly suppress T-lymphocyte proliferation in vitro. M-MDSCs collected from silica-treated mice also express transforming growth factor (TGF)-ß1, which stimulates lung fibroblasts to release tissue inhibitor of metalloproteinase (TIMP)-1, an inhibitor of metalloproteinase collagenolytic activity. By using LysMCreCCR2loxP/loxP mice, we show that limiting CCR2+ M-MDSC accumulation reduces the pulmonary contents of TGF-ß1, TIMP-1 and collagen after silica treatment. M-MDSCs do not differentiate into lung macrophages, granulocytes or fibrocytes during pulmonary fibrogenesis. Collectively, our data indicate that M-MDSCs contribute to lung fibrosis by specifically promoting a non-degrading collagen microenvironment. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Monócitos/metabolismo , Células Supressoras Mieloides/citologia , Fibrose Pulmonar/metabolismo , Receptores CCR2/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Proliferação de Células/fisiologia , Colágeno/metabolismo , Pulmão/patologia , Ativação Linfocitária/fisiologia , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/patologia
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