Specific depletion reveals a novel role for neutrophil-mediated protection in the liver during Listeria monocytogenes infection.

Specific depletion reveals a novel role for neutrophil-mediated protection in the liver during Listeria monocytogenes infection.
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DOI:
10.1002/eji.201041363
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发表时间:
2011-09
影响因子:
5.4
通讯作者:
Berg, Rance E.
Berg, Rance E.
中科院分区:
医学3区
文献类型:
--
作者:
Carr, Karen D.;Sieve, Amy N.;Indramohan, Mohanalaxmi;Break, Timothy J.;Lee, Suheung;Berg, Rance E.

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先前的研究表明,中性粒细胞是多种病原微生物感染期间抵抗所必需的。然而,这些研究中使用的消耗抗体结合Ly 6 G和Ly 6C(抗Gr-1;克隆RB 6 - 8 C5)。这种抗体已被证明不仅消耗嗜中性粒细胞,而且还消耗单核细胞和CD 8 T细胞的子集。最近,已经表征了针对Ly 6 G的抗体,其特异性地消耗嗜中性粒细胞。在本研究中,中性粒细胞耗尽使用抗Ly 6 G的抗体在感染细胞内细菌,单核细胞增生李斯特菌(LM)。我们的数据表明,中性粒细胞耗竭的小鼠比抗Gr-1耗竭的小鼠对感染的敏感性低得多。虽然嗜中性粒细胞是清除LM所必需的,但它们在肝脏和高剂量细菌挑战期间的重要性更明显。此外,我们证明中性粒细胞介导的保护作用是由于TNF-α的产生,而不是IFN-γ。此外,在LM感染期间,单核细胞的募集或适应性T细胞应答的产生不需要中性粒细胞。这些研究强调了嗜中性粒细胞在LM感染期间的重要性,并且还表明嗜中性粒细胞的消耗比所有表达Gr-1的细胞群的消耗对宿主的危害更小。
Previous studies have suggested that neutrophils are required for resistance during infection with multiple pathogenic microorganisms. However, the depleting antibody used in those studies binds to both Ly6G and Ly6C (anti-Gr-1; clone RB6-8C5). This antibody has been shown to not only deplete neutrophils, but also monocytes, and a subset of CD8 T cells. Recently, an antibody against Ly6G has been characterized which specifically depletes neutrophils. In the present study, neutrophils are depleted using the antibody against Ly6G during infection with the intracellular bacterium, Listeria monocytogenes (LM). Our data show that neutrophil depleted mice are much less susceptible to infection than mice depleted with anti-Gr-1. Although neutrophils are required for clearance of LM, their importance is more pronounced in the liver and during a high-dose bacterial challenge. Furthermore, we demonstrate that protection mediated by neutrophils is due to production of TNF-α, but not IFN-γ. Additionally, neutrophils are not required for the recruitment of monocytes or the generation of adaptive T cell responses during LM infection. These studies highlight the importance of neutrophils during LM infection, and also indicate that depletion of neutrophils is less detrimental to the host than depletion of all Gr-1 expressing cell populations.
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