The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice.

The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice.
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小鼠流感病毒感染期间中性粒细胞在上呼吸道和下呼吸道中的作用。

DOI:
10.1186/1465-9921-9-57
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发表时间:
2008-08-01
影响因子:
5.8
通讯作者:
Reading, Patrick C.
Reading, Patrick C.
中科院分区:
医学2区
文献类型:
--
作者:
Tate, Michelle D.;Brooks, Andrew G.;Reading, Patrick C.

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中性粒细胞已被证明在抵抗高毒力和小鼠适应的流感病毒株的宿主防御中发挥作用,但尚不清楚在感染其他病毒株时,有效的中性粒细胞反应是否是缓解疾病严重程度的重要因素。在这项研究中,我们研究了中性粒细胞在H3N2亚型流感病毒株HKx31感染小鼠过程中的作用,以确定中性粒细胞在感染早期阶段和感染后期在流感病毒从呼吸道清除中的作用。用抗Gr-1单抗(MAb)RB6-8C5鉴定未感染和流感病毒感染小鼠上(鼻)、下(肺)呼吸道的中性粒细胞,以及(Ii)在流感病毒感染前和感染过程中清除中性粒细胞。流感病毒感染后,中性粒细胞迅速被招募到上呼吸道和下呼吸道。我们证明了使用单抗RB6-8C5去除C57BL/6(B6)小鼠的中性粒细胞是复杂的,因为这种单抗能够直接与病毒特异性的CD8+T细胞结合。因此,我们利用CD8+T细胞缺陷的B6.TAP-/-小鼠研究了中性粒细胞在感染早期和晚期的作用。用低剂量流感病毒感染B6-TAP-/-小鼠,对照动物没有引起临床疾病,但RB6-8C5治疗导致体重显著下降,严重的临床疾病,并促进病毒在整个呼吸道的复制。在感染的早期和后期,中性粒细胞在限制流感病毒复制方面发挥了关键作用。此外,在缺乏有效的中性粒细胞反应的情况下,中等毒力的病毒株可能会导致严重的临床疾病。
Neutrophils have been shown to play a role in host defence against highly virulent and mouse-adapted strains of influenza virus, however it is not clear if an effective neutrophil response is an important factor moderating disease severity during infection with other virus strains. In this study, we have examined the role of neutrophils during infection of mice with influenza virus strain HKx31, a virus strain of the H3N2 subtype and of moderate virulence for mice, to determine the role of neutrophils in the early phase of infection and in clearance of influenza virus from the respiratory tract during the later phase of infection. The anti-Gr-1 monoclonal antibody (mAb) RB6-8C5 was used to (i) identify neutrophils in the upper (nasal tissues) and lower (lung) respiratory tract of uninfected and influenza virus-infected mice, and (ii) deplete neutrophils prior to and during influenza virus infection of mice. Neutrophils were rapidly recruited to the upper and lower airways following influenza virus infection. We demonstrated that use of mAb RB6-8C5 to deplete C57BL/6 (B6) mice of neutrophils is complicated by the ability of this mAb to bind directly to virus-specific CD8+ T cells. Thus, we investigated the role of neutrophils in both the early and later phases of infection using CD8+ T cell-deficient B6.TAP-/- mice. Infection of B6.TAP-/- mice with a low dose of influenza virus did not induce clinical disease in control animals, however RB6-8C5 treatment led to profound weight loss, severe clinical disease and enhanced virus replication throughout the respiratory tract. Neutrophils play a critical role in limiting influenza virus replication during the early and later phases of infection. Furthermore, a virus strain of moderate virulence can induce severe clinical disease in the absence of an effective neutrophil response.
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DOI: 10.1128/jvi.01210-07
发表时间: 2008-03-01
影响因子: 5.4
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