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皮肤中趋化因子 CCL2、CCL4、CCL5、CCL21 和 CXCL8 的高表达与犬内脏利什曼病寄生虫密度相关。

Higher expression of CCL2, CCL4, CCL5, CCL21, and CXCL8 chemokines in the skin associated with parasite density in canine visceral leishmaniasis.

机构信息

Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brasil.

出版信息

PLoS Negl Trop Dis. 2012;6(4):e1566. doi: 10.1371/journal.pntd.0001566. Epub 2012 Apr 10.

DOI:10.1371/journal.pntd.0001566
PMID:22506080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3323520/
Abstract

BACKGROUND

The immune response in the skin of dogs infected with Leishmania infantum is poorly understood, and limited studies have described the immunopathological profile with regard to distinct levels of tissue parasitism and the clinical progression of canine visceral leishmaniasis (CVL).

METHODOLOGY/PRINCIPAL FINDINGS: A detailed analysis of inflammatory cells (neutrophils, eosinophils, mast cells, lymphocytes, and macrophages) as well as the expression of chemokines (CCL2, CCL4, CCL5, CCL13, CCL17, CCL21, CCL24, and CXCL8) was carried out in dermis skin samples from 35 dogs that were naturally infected with L. infantum. The analysis was based on real-time polymerase chain reaction (PCR) in the context of skin parasitism and the clinical status of CVL. We demonstrated increased inflammatory infiltrate composed mainly of mononuclear cells in the skin of animals with severe forms of CVL and high parasite density. Analysis of the inflammatory cell profile of the skin revealed an increase in the number of macrophages and reductions in lymphocytes, eosinophils, and mast cells that correlated with clinical progression of the disease. Additionally, enhanced parasite density was correlated with an increase in macrophages and decreases in eosinophils and mast cells. The chemokine mRNA expression demonstrated that enhanced parasite density was positively correlated with the expression of CCL2, CCL4, CCL5, CCL21, and CXCL8. In contrast, there was a negative correlation between parasite density and CCL24 expression.

CONCLUSIONS/SIGNIFICANCE: These findings represent an advance in the knowledge about skin inflammatory infiltrates in CVL and the systemic consequences. Additionally, the findings may contribute to the design of new and more efficient prophylactic tools and immunological therapies against CVL.

摘要

背景

犬感染利什曼原虫后皮肤的免疫反应尚不清楚,仅有有限的研究描述了不同组织寄生虫水平和犬内脏利什曼病(CVL)临床进展的免疫病理学特征。

方法/主要发现:对 35 只自然感染利什曼原虫的犬的皮肤真皮样本进行了炎症细胞(中性粒细胞、嗜酸性粒细胞、肥大细胞、淋巴细胞和巨噬细胞)以及趋化因子(CCL2、CCL4、CCL5、CCL13、CCL17、CCL21、CCL24 和 CXCL8)表达的详细分析。分析基于皮肤寄生虫和 CVL 临床状况的实时聚合酶链反应(PCR)。我们发现在严重 CVL 形式和高寄生虫密度的动物皮肤中,炎症浸润主要由单核细胞组成。皮肤炎症细胞分析显示,巨噬细胞数量增加,淋巴细胞、嗜酸性粒细胞和肥大细胞减少,与疾病的临床进展相关。此外,寄生虫密度增加与巨噬细胞增加和嗜酸性粒细胞和肥大细胞减少相关。趋化因子 mRNA 表达表明,增强的寄生虫密度与 CCL2、CCL4、CCL5、CCL21 和 CXCL8 的表达呈正相关。相反,寄生虫密度与 CCL24 表达呈负相关。

结论/意义:这些发现代表了对 CVL 皮肤炎症浸润和全身后果的认识的进步。此外,这些发现可能有助于设计针对 CVL 的新的、更有效的预防性工具和免疫治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d7/3323520/7ca4a56e0a4b/pntd.0001566.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d7/3323520/a490838f67ea/pntd.0001566.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d7/3323520/1bcfb1216649/pntd.0001566.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d7/3323520/e485c29d4eae/pntd.0001566.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d7/3323520/7ca4a56e0a4b/pntd.0001566.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d7/3323520/a490838f67ea/pntd.0001566.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d7/3323520/1bcfb1216649/pntd.0001566.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d7/3323520/e485c29d4eae/pntd.0001566.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5d7/3323520/7ca4a56e0a4b/pntd.0001566.g004.jpg

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