IL-21 signaling promotes the establishment of KSHV infection in human tonsil lymphocytes by increasing differentiation and targeting of plasma cells.
IL-21 signaling promotes the establishment of KSHV infection in human tonsil lymphocytes by increasing differentiation and targeting of plasma cells.
复制标题
DOI：
10.3389/fimmu.2022.1010274
复制
发表时间：
2022
影响因子：
7.3
通讯作者：
Totonchy, Jennifer
中科院分区：
文献类型：
--
作者：
Alomari, Nedaa;Totonchy, Jennifer
影响卡波济肉瘤相关疱疹病毒（KSHV）传播的因素和人类免疫系统中KSHV感染的早期阶段仍然缺乏特征。已知KSHV广泛操纵宿主免疫系统和细胞因子环境，并且已知细胞因子影响KSHV相关疾病的进展。我们以前的工作确定了KSHV感染的早期靶向浆细胞。在这项研究中，我们研究是否IL-21，一种已知深刻影响浆细胞命运的细胞因子，影响B淋巴细胞中KSHV感染的早期阶段。利用我们独特的体外KSHV感染扁桃体淋巴细胞的模型，我们研究了IL-21补充、IL-21中和、IL-21受体在B细胞亚群上的分布以及IL-21分泌性T细胞亚群对人B细胞中建立KSHV感染的影响。我们发现IL-21信号通过促进总浆细胞数和早在感染后3天增加浆细胞中的KSHV感染来促进KSHV感染。我们进一步证明KSHV感染和IL-21治疗对浆细胞频率的协同作用是由于新浆细胞从幼稚B细胞前体分化而来。我们检查了扁桃体样本中分泌IL-21的T细胞，并确定产生IL-21的CD 8+中央记忆T细胞与浆细胞频率和KSHV对浆细胞的靶向相关。这些结果证明了新的发现，即新浆细胞的分化参与B细胞中KSHV感染的早期阶段，并且IL-21信号传导可以增强这种作用，从而在早期时间点增加KSHV感染的总体幅度。这些结果表明，IL-21信号转导代表了建立KSHV感染的宿主水平易感性因素。
Factors influencing Kaposi’s sarcoma-associated herpesvirus (KSHV) transmission and the early stages of KSHV infection in the human immune system remain poorly characterized. KSHV is known to extensively manipulate the host immune system and the cytokine milieu, and cytokines are known to influence the progression of KSHV-associated diseases. Our previous work identified the early targeting of plasma cells for KSHV infection. In this study, we examine whether IL-21, a cytokine known to profoundly influence plasma cell fate, influences the early stages of KSHV infection in B lymphocytes. Using our unique model of ex vivo KSHV infection in tonsil lymphocytes, we investigate the influence of IL-21 supplementation, IL-21 neutralization, the distribution of IL-21 receptor on B cell subsets and IL-21 secreting T cell subsets on the establishment of KSHV infection in human B cells. We show that IL-21 signaling promotes KSHV infection by promoting both total plasma cell numbers and increasing KSHV infection in plasma cells as early as 3 days post-infection. We further demonstrate that the synergistic effect of KSHV infection and IL-21 treatment on plasma cell frequencies is due to differentiation of new plasma cells from naïve B cell precursors. We examine T cells secreting IL-21 in our tonsil specimens and determine that IL-21 producing CD8+ central memory T cells are correlated with plasma cell frequencies and KSHV targeting of plasma cells. These results demonstrate the novel finding that differentiation of new plasma cells is involved in the early stages of KSHV infection in B cells, and that IL-21 signaling can potentiate this effect thereby increasing the overall magnitude of KSHV infection at early timepoints. These results suggest that IL-21 signaling represents a host-level susceptibility factor for the establishment of KSHV infection.
登录
查看更多内容
影响因子：
5.4
作者：
Laichalk, LL;Thorley-Lawson, DA
通讯作者：
Thorley-Lawson, DA
影响因子：
3.7
作者：
Chang, J;Renne, R;Ganem, D
通讯作者：
Ganem, D
DOI：
10.3390/v12101097
发表时间：
2020-09-28
期刊：
Viruses
影响因子：
--
作者：
Alomari N;Totonchy J
通讯作者：
Totonchy J
影响因子：
5.4
作者：
Quigley, Maire F.;Gonzalez, Veronica D.;Sandberg, Johan K.
通讯作者：
Sandberg, Johan K.
影响因子：
64.8
作者：
Parrish-Novak, J;Dillon, SR;Foster, D
通讯作者：
Foster, D