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中性粒细胞抑制布鲁氏菌病中的适应性免疫。

Neutrophils Dampen Adaptive Immunity in Brucellosis.

机构信息

Programa de Investigación en Enfermedades Tropicales (PIET), Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.

Departamento de Patología, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.

出版信息

Infect Immun. 2019 Apr 23;87(5). doi: 10.1128/IAI.00118-19. Print 2019 Mar.

Abstract

organisms are intracellular stealth pathogens of animals and humans. The bacteria overcome the assault of innate immunity at early stages of an infection. Removal of polymorphonuclear neutrophils (PMNs) at the onset of adaptive immunity against favored bacterial elimination in mice. This was associated with higher levels of interferon gamma (IFN-γ) and a higher proportion of cells expressing interleukin 6 (IL-6) and inducible nitric oxide synthase (iNOS), compatible with M1 macrophages, in PMN-depleted -infected (PMNd-) mice. At later times in the acute infection phase, the amounts of IFN-γ fell while IL-6, IL-10, and IL-12 became the predominant cytokines in PMNd- mice. IL-4, IL-1β, and tumor necrosis factor alpha (TNF-α) remained at background levels at all times of the infection. Depletion of PMNs at the acute stages of infection promoted the premature resolution of spleen inflammation. The efficient removal of bacteria in the PMNd- mice was not due to an increase of antibodies, since the immunoglobulin isotype responses to antigens were dampened. Anti- antibodies abrogated the production of IL-6, IL-10, and IL-12 but did not affect the levels of IFN-γ at later stages of infection in PMNd- mice. These results demonstrate that PMNs have an active role in modulating the course of infection after the adaptive immune response has already developed.

摘要

病原体是动物和人类细胞内的隐匿性病原体。细菌在感染的早期阶段克服了先天免疫的攻击。在针对 的适应性免疫开始时去除多形核中性粒细胞(PMN),有利于在小鼠中消除细菌。这与更高水平的干扰素γ(IFN-γ)和更高比例表达白细胞介素 6(IL-6)和诱导型一氧化氮合酶(iNOS)的细胞有关,与 PMN 耗竭感染(PMNd-)小鼠中的 M1 巨噬细胞相容。在急性感染阶段的后期,IFN-γ的量下降,而 IL-6、IL-10 和 IL-12 成为 PMNd-小鼠中的主要细胞因子。IL-4、IL-1β 和肿瘤坏死因子α(TNF-α)在感染的所有时间都保持在背景水平。在感染的急性阶段耗尽 PMN 可促进脾脏炎症的过早消退。PMNd-小鼠中细菌的有效清除并不是由于抗体的增加,因为针对 抗原的免疫球蛋白同种型反应受到抑制。抗- 抗体消除了 IL-6、IL-10 和 IL-12 的产生,但不影响 PMNd-小鼠感染后期 IFN-γ的水平。这些结果表明,PMN 在适应性免疫反应已经发展之后,在调节 感染的过程中具有积极作用。

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