S100A4+ macrophages facilitate zika virus invasion and persistence in the seminiferous tubules via interferon-gamma mediation.
S100A4+ macrophages facilitate zika virus invasion and persistence in the seminiferous tubules via interferon-gamma mediation.
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S100A4巨噬细胞通过干扰素-γ介导促进寨卡病毒入侵并在生精小管中持续存在
DOI：
10.1371/journal.ppat.1009019
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发表时间：
2020-12
期刊：
影响因子：
6.7
通讯作者：
An J
中科院分区：
文献类型：
--
作者：
Yang W;Wu YH;Liu SQ;Sheng ZY;Zhen ZD;Gao RQ;Cui XY;Fan DY;Qin ZH;Zheng AH;Wang PG;An J
睾丸侵入和持久性是寨卡病毒（ZIKV）的特征，但其机制仍不清楚。在此，我们显示S100 A4+巨噬细胞（对ZIKV感染具有易感性的骨髓巨噬细胞亚群）促进ZIKV侵袭和在生精小管中的持久性。在ZIKV感染的小鼠中，S100 A4+巨噬细胞特异性募集到睾丸的间质空间中并分化成表达干扰素-γ的M1巨噬细胞。在干扰素-γ介导下，S100 A4+巨噬细胞下调Claudin-1的表达，并诱导Claudin-1从胞浆重新分布到细胞核，从而增加血睾屏障的通透性，促进S100 A4+巨噬细胞侵入曲细精管。管腔内S100 A4+巨噬细胞与CD 8 + T细胞分离，因此帮助ZIKV逃避细胞免疫。结果，即使当生精细胞消失时，ZIKV继续在管腔内S100 A4+巨噬细胞中复制。S100 A4或干扰素-γ信号传导中的缺陷都减少了生精小管中的ZIKV感染。这些结果证明了S100 A4+巨噬细胞在睾丸中的ZIKV感染中的关键作用。
Testicular invasion and persistence are features of Zika virus (ZIKV), but their mechanisms are still unknown. Here, we showed that S100A4+ macrophages, a myeloid macrophage subpopulation with susceptibility to ZIKV infection, facilitated ZIKV invasion and persistence in the seminiferous tubules. In ZIKV-infected mice, S100A4+ macrophages were specifically recruited into the interstitial space of testes and differentiated into interferon-γ-expressing M1 macrophages. With interferon-γ mediation, S100A4+ macrophages down-regulated Claudin-1 expression and induced its redistribution from the cytosol to nucleus, thus increasing the permeability of the blood-testis barrier which facilitated S100A4+ macrophages invasion into the seminiferous tubules. Intraluminal S100A4+ macrophages were segregated from CD8+ T cells and consequently helped ZIKV evade cellular immunity. As a result, ZIKV continued to replicate in intraluminal S100A4+ macrophages even when the spermatogenic cells disappeared. Deficiencies in S100A4 or interferon-γ signaling both reduced ZIKV infection in the seminiferous tubules. These results demonstrated crucial roles of S100A4+ macrophages in ZIKV infection in testes.
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