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

Gonzalez-Tafoya Eddie; Diupotex Mariana; Zamora-Chimal Jaime; Salaiza-Suazo Norma; Ruiz-Remigio Adriana; Becker Ingeborg

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

机译：TNF通过PD-L1上调导致小鼠慢性L. Mexicana感染的T细胞耗尽

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Leishmania mexicana can produce chronic infections leading to exhausted T cell phenotypes, mediated by PD-1/PD-L1. Little is known on mechanisms that induce these inhibitory molecules in chronic leishmaniasis. We analyzed factors that contribute to exhausted phenotypes in chronic L. mexicana infections of mice. Our results show that draining lymph node cells express enhanced levels of PD-1/PD-L1. T lymphocytes producing low cytokine levels were also found. L. mexicana infection of dendritic cells (DCs) produced elevated amounts of TNF and showed up-regulation of PD-L1 expression. We provide evidence that T cells of chronic L. mexicana infections in mice are functionally exhausted due to chronic TNF production, which leads to PD-L1 up-regulation in DCs. We conclude that TNF has a fundamental role in promoting T cell exhaustion during chronic L. mexicana infections, which contributes to the inability of T cells to proliferate and produce pro-inflammatory cytokines, thus favoring disease progression.

机译：墨西哥利什曼原虫可通过PD-1/PD-L1介导产生导致T细胞表型衰竭的慢性感染。在慢性利什曼病中诱导这些抑制性分子的机制知之甚少。我们分析了导致小鼠慢性墨西哥乳杆菌感染衰竭表型的因素。我们的研究结果表明，引流淋巴结细胞表达PD-1/PD-L1水平增强。还发现产生低细胞因子水平的T淋巴细胞。墨西哥乳杆菌感染树突状细胞（DC）后产生大量TNF，并显示PD-L1表达上调。我们提供的证据表明，小鼠慢性墨西哥乳杆菌感染的T细胞由于慢性TNF产生而功能衰竭，这导致DC中PD-L1上调。我们的结论是，在慢性墨西哥乳杆菌感染期间，TNF在促进T细胞衰竭方面起着基础性作用，这导致T细胞无法增殖和产生促炎细胞因子，从而有利于疾病的进展。

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来源
《Cellular immunology》 |2020年第1期|共10页
作者
Gonzalez-Tafoya Eddie; Diupotex Mariana; Zamora-Chimal Jaime; Salaiza-Suazo Norma; Ruiz-Remigio Adriana; Becker Ingeborg;
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作者单位

Univ Nacl Autonoma Mexico Hosp Gen Mexico Fac Med Unidad Invest Med Expt Dr Balmis 148 Ciudad;

Univ Nacl Autonoma Mexico Hosp Gen Mexico Fac Med Unidad Invest Med Expt Dr Balmis 148 Ciudad;

Univ Nacl Autonoma Mexico Hosp Gen Mexico Fac Med Unidad Invest Med Expt Dr Balmis 148 Ciudad;

Univ Nacl Autonoma Mexico Hosp Gen Mexico Fac Med Unidad Invest Med Expt Dr Balmis 148 Ciudad;

Univ Nacl Autonoma Mexico Hosp Gen Mexico Fac Med Unidad Invest Med Expt Dr Balmis 148 Ciudad;

Univ Nacl Autonoma Mexico Hosp Gen Mexico Fac Med Unidad Invest Med Expt Dr Balmis 148 Ciudad;

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原文格式 PDF
正文语种 eng
中图分类细胞生物学;
关键词
Leishmania mexicana; Chronic infection; Mouse model; Exhausted phenotype; TNF; PD-1; PD-L1;

机译：Leishmania Mexicana;慢性感染;小鼠模型;耗尽的表型;TNF;PD-1;PD-L1;

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

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