NK cell responses to simian immunodeficiency virus vaginal exposure in naive and vaccinated rhesus macaques.
NK cell responses to simian immunodeficiency virus vaginal exposure in naive and vaccinated rhesus macaques.
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DOI：
10.4049/jimmunol.1400417
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发表时间：
2014-07-01
期刊：
影响因子：
--
通讯作者：
Haase AT
中科院分区：
文献类型：
--
作者：
Shang L;Smith AJ;Duan L;Perkey KE;Qu L;Wietgrefe S;Zupancic M;Southern PJ;Masek-Hammerman K;Reeves RK;Johnson RP;Haase AT
NK 细胞对 HIV/SIV 感染的反应已在急性和慢性感染患者/猴子中得到充分研究，但人们对病毒传播过程中的 NK 细胞知之甚少，特别是在粘膜组织中。在此，我们报告了一项系统研究，研究了恒河猴雌性生殖道 (FRT) 中 NK 细胞对高剂量阴道暴露于 SIVmac251 的反应。阴道接种后，少量 NK 细胞被招募到 FRT 粘膜中。粘膜 NK 细胞的流入先于局部病毒复制，并在一周时达到峰值，因此处于适当的时间范围内，可以控制入口处感染细胞数量的增加。然而，NK 细胞的数量远远超过了招募的靶细胞，这些靶细胞促进了局部病毒的扩张，并且在过渡区和邻近宫颈内膜的受感染创始人群体扩张的主要部位与 SIV RNA+ 细胞在空间上分离。 FRT粘膜中的NK细胞数量在第二周迅速减少，与局部SIV RNA+细胞的峰值呈反比关系。粘膜 NK 细胞产生 IFN-γ 和 MIP-1α/CCL3，但缺乏多种激活和细胞毒性标志物，这与接种诱导的抑制性配体 HLA-E 上调和激活受体 CD122/IL2Rβ 下调相关。对接种 SIVΔnef 的猴子进行的检查表明，NK 细胞募集到生殖器粘膜并不参与疫苗诱导的针对阴道攻击的保护。总之，我们的结果表明 NK 细胞在 FRT 对抗阴道攻击的防御中最多发挥有限的作用。
NK cell responses to HIV/SIV infection have been well studied in acute and chronic infected patients/monkeys, but little is known about NK cells during viral transmission, particularly in mucosal tissues. Here we report a systematic study of NK cell responses to high-dose vaginal exposure to SIVmac251 in the rhesus macaque female reproductive tract (FRT). Small numbers of NK cells were recruited into the FRT mucosa following vaginal inoculation. The influx of mucosal NK cells preceded local virus replication and peaked at one week, and was thus in an appropriate time frame to control an expanding population of infected cells at the portal of entry. However, NK cells were greatly outnumbered by recruited target cells that fuel local virus expansion, and were spatially dissociated from SIV RNA+ cells at the major site of expansion of infected founder populations in the transition zone and adjoining endocervix. The number of NK cells in the FRT mucosa rapidly decreased in the second week, in an inverse relationship to the peak of local SIV RNA+ cells. Mucosal NK cells produced IFN-γ and MIP-1α/CCL3, but lacked several markers of activation and cytotoxicity, and this was correlated with inoculum-induced upregulation of the inhibitory ligand HLA-E and downregulation of the activating receptor CD122/IL2Rβ. Examination of SIVΔnef-vaccinated monkeys suggested that recruitment of NK cells to the genital mucosa was not involved in vaccine-induced protection from vaginal challenge. In summary, our results suggest that NK cells play at most a limited role in defenses in the FRT against vaginal challenge.
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影响因子：
5.4
作者：
Reeves, R. Keith;Evans, Tristan I.;Johnson, R. Paul
通讯作者：
Johnson, R. Paul
影响因子：
8
作者：
Sips, M.;Sciaranghella, G.;Alter, G.
通讯作者：
Alter, G.
影响因子：
5.4
作者：
Johnson, RP;Lifson, JD;Desrosiers, RC
通讯作者：
Desrosiers, RC
影响因子：
20.3
作者：
Mavilio, D;Benjamin, J;Fauci, AS
通讯作者：
Fauci, AS
影响因子：
20.3
作者：
Reeves, R. Keith;Gillis, Jacqueline;Johnson, R. Paul
通讯作者：
Johnson, R. Paul