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针对皮肤利什曼病的宿主导向疗法。

Host-Directed Therapies for Cutaneous Leishmaniasis.

机构信息

Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH, United States.

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States.

出版信息

Front Immunol. 2021 Mar 26;12:660183. doi: 10.3389/fimmu.2021.660183. eCollection 2021.


DOI:10.3389/fimmu.2021.660183
PMID:33841444
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8032888/
Abstract

Cutaneous leishmaniasis exhibits a wide spectrum of clinical presentations from self-resolving infections to severe chronic disease. Anti-parasitic drugs are often ineffective in the most severe forms of the disease, and in some cases the magnitude of the disease can result from an uncontrolled inflammatory response rather than unrestrained parasite replication. In these patients, host-directed therapies offer a novel approach to improve clinical outcome. Importantly, there are many anti-inflammatory drugs with known safety and efficacy profiles that are currently used for other inflammatory diseases and are readily available to be used for leishmaniasis. However, since leishmaniasis consists of a wide range of clinical entities, mediated by a diverse group of leishmanial species, host-directed therapies will need to be tailored for specific types of leishmaniasis. There is now substantial evidence that host-directed therapies are likely to be beneficial beyond autoimmune diseases and cancer and thus should be an important component in the armamentarium to modulate the severity of cutaneous leishmaniasis.

摘要

皮肤利什曼病的临床表现范围广泛,从自限性感染到严重的慢性疾病都有。在疾病的最严重形式中,抗寄生虫药物往往无效,在某些情况下,疾病的严重程度可能是由于不受控制的炎症反应而不是寄生虫不受限制的复制。在这些患者中,宿主定向治疗为改善临床结果提供了一种新方法。重要的是,有许多具有已知安全性和疗效特征的抗炎药物目前用于治疗其他炎症性疾病,并且很容易用于治疗利什曼病。然而,由于利什曼病由广泛的临床实体组成,由多种利什曼原虫介导,因此宿主定向治疗需要针对特定类型的利什曼病进行调整。现在有大量证据表明,宿主定向治疗可能不仅对自身免疫性疾病和癌症有益,而且应该成为调节皮肤利什曼病严重程度的武器库中的一个重要组成部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e881/8032888/5260cb42d2c0/fimmu-12-660183-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e881/8032888/a75d451bf9ec/fimmu-12-660183-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e881/8032888/5260cb42d2c0/fimmu-12-660183-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e881/8032888/a75d451bf9ec/fimmu-12-660183-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e881/8032888/5260cb42d2c0/fimmu-12-660183-g002.jpg

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[2]
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本文引用的文献

[1]
PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis.

Front Immunol. 2021

[2]
Understanding adverse events of immunotherapy: A mechanistic perspective.

J Exp Med. 2021-1-4

[3]
Risk factors for antimony treatment failure in American Cutaneous Leishmaniasis in Northwestern-Argentina.

PLoS Negl Trop Dis. 2021-1

[4]
TNF contributes to T-cell exhaustion in chronic L. mexicana infections of mice through PD-L1 up-regulation.

Cell Immunol. 2020-12

[5]
Tissue Damage in Human Cutaneous Leishmaniasis: Correlations Between Inflammatory Cells and Molecule Expression.

Front Cell Infect Microbiol. 2020-7-14

[6]
Granzyme B Inhibition by Tofacitinib Blocks the Pathology Induced by CD8 T Cells in Cutaneous Leishmaniasis.

J Invest Dermatol. 2021-3

[7]
Impaired Th1 Response Is Associated With Therapeutic Failure in Patients With Cutaneous Leishmaniasis Caused by Leishmania braziliensis.

J Infect Dis. 2021-2-13

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A guide to cancer immunotherapy: from T cell basic science to clinical practice.

Nat Rev Immunol. 2020-5-20

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Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8 T cells in human cutaneous leishmaniasis.

Immunology. 2020-1-26

[10]
Immunotherapy using anti-PD-1 and anti-PD-L1 in Leishmania amazonensis-infected BALB/c mice reduce parasite load.

Sci Rep. 2019-12-30

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