Aedes aegypti saliva alters leukocyte recruitment and cytokine signaling by antigen-presenting cells during West Nile virus infection.
Aedes aegypti saliva alters leukocyte recruitment and cytokine signaling by antigen-presenting cells during West Nile virus infection.
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DOI：
10.1371/journal.pone.0011704
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发表时间：
2010-07-22
期刊：
影响因子：
3.7
通讯作者：
Higgs S
中科院分区：
文献类型：
--
作者：
Schneider BS;Soong L;Coffey LL;Stevenson HL;McGee CE;Higgs S
西尼罗河病毒（WNV）是通过蚊子吸血传播的。因此，首先接触西尼罗河病毒的脊椎动物细胞是皮肤中的细胞，然后是引流淋巴结中的细胞。巨噬细胞和树突状细胞是宿主防御西尼罗河病毒感染的关键早期反应者，不仅因为它们在协调免疫反应中的作用，还因为它们作为早期外周病毒复制位点的重要性。抗原提呈细胞（APC）信号对宿主抗病毒反应和疾病严重程度有深远的影响。在传播过程中，西尼罗河病毒与蚊子唾液密切相关。由于蚊子唾液影响炎症和免疫反应的能力，以及了解WNV感染早期事件的重要性，我们研究了蚊子唾液是否会改变虫媒病毒感染期间的APC信号传导，以及当WNV感染开始时蚊子唾液是否会改变细胞募集。因此，用培养的树突状细胞和巨噬细胞进行实验，流式细胞术用于表征早期感染期间皮肤和淋巴结中的浸润细胞类型，并采用实时RT-PCR评估病毒和细胞因子水平。我们的体外研究结果表明，蚊子唾液显着降低巨噬细胞中干扰素-β和诱导型一氧化氮合酶的表达（分别高达50%和70%），同时瞬时增强白细胞介素-10（IL-10）的表达。体内结果表明，蚊子喂养的主要作用是显着减少T细胞的募集，导致单独暴露于WNV的小鼠的接种部位具有高达2.8倍的T细胞，因为在蚊子唾液的存在下感染小鼠。这些细胞群的变化与皮肤和引流淋巴结中IL-10和WNV的显著升高（分别高达4.0和10倍）相关。这些结果表明，蚊子唾液失调APC抗病毒信号，并揭示了一个可能的机制，通过减少T淋巴细胞和抗病毒活性在接种部位，易感细胞类型的丰度升高，并伴随着增加免疫调节活性的IL-10的蚊子唾液介导的WNV疾病的观察增强。
West Nile virus (WNV) is transmitted during mosquito bloodfeeding. Consequently, the first vertebrate cells to contact WNV are cells in the skin, followed by those in the draining lymph node. Macrophages and dendritic cells are critical early responders in host defense against WNV infection, not just because of their role in orchestrating the immune response, but also because of their importance as sites of early peripheral viral replication. Antigen-presenting cell (APC) signals have a profound effect on host antiviral responses and disease severity. During transmission, WNV is intimately associated with mosquito saliva. Due to the ability of mosquito saliva to affect inflammation and immune responses, and the importance of understanding early events in WNV infection, we investigated whether mosquito saliva alters APC signaling during arbovirus infection, and if alterations in cell recruitment occur when WNV infection is initiated with mosquito saliva. Accordingly, experiments were performed with cultured dendritic cells and macrophages, flow cytometry was used to characterize infiltrating cell types in the skin and lymph nodes during early infection, and real-time RT-PCR was employed to evaluate virus and cytokine levels. Our in vitro results suggest that mosquito saliva significantly decreases the expression of interferon-β and inducible nitric oxide synthase in macrophages (by as much as 50 and 70%, respectively), whilst transiently enhancing interleukin-10 (IL-10) expression. In vivo results indicate that the predominate effect of mosquito feeding is to significantly reduce the recruitment of T cells, leading the inoculation site of mice exposed to WNV alone to have up to 2.8 fold more t cells as mice infected in the presence of mosquito saliva. These shifts in cell population are associated with significantly elevated IL-10 and WNV (up to 4.0 and 10 fold, respectively) in the skin and draining lymph nodes. These results suggest that mosquito saliva dysregulates APC antiviral signaling, and reveal a possible mechanism for the observed enhancement of WNV disease mediated by mosquito saliva via a reduction of T lymphocyte and antiviral activity at the inoculation site, an elevated abundance of susceptible cell types, and a concomitant increase in immunoregulatory activity of IL-10.
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影响因子：
--
作者：
Macaluso, KR;Wikel, SK
通讯作者：
Wikel, SK
影响因子：
2.7
作者：
ANJILI, CO;MBATI, PA;KOECH, DK
通讯作者：
KOECH, DK
影响因子：
3.1
作者：
Kuthejlová, M;Kopecky, J;Macela, A
通讯作者：
Macela, A
DOI：
10.4269/ajtmh.2006.75.532
发表时间：
2006-09-01
影响因子：
3.3
作者：
Bishop, Jeanette V.;Mejia, J. Santiago;Titus, Richard G.
通讯作者：
Titus, Richard G.
影响因子：
5.5
作者：
Lobigs, M;Pavy, M;Hall, R
通讯作者：
Hall, R