Amir Mohammed, Aqdas Mohammad, Nadeem Sajid, Siddiqui Kaneez F, Khan Nargis, Sheikh Javaid A, Agrewala Javed N
Immunology Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India.
Front Immunol. 2017 May 30;8:624. doi: 10.3389/fimmu.2017.00624. eCollection 2017.
It is instrumental for the to persist within its host in dormancy. represses most of its metabolic machinery during latency, but upregulates the expression of latency-associated protein alpha-crystallin protein (Acr1). Therefore, it is imperative to understand how throughout dormancy, employs Acr1 to regulate the host immunity. This study reveals that Acr1 exhibits divergent effect on the pre- and post-maturation stages of dendritic cells (DCs). In the current study, we demonstrate that early encounter of bone marrow cells with Acr1 while differentiating into DCs (AcrDC), leads to impairment in their maturation. In contrast, when exposed to Acr1 after maturation (AcrDC), DCs show augmentation in their activity, secretion of TNF-α, IL-12, IL-6, and activation of T cells. Additionally, AcrDC promoted the polarization of naïve CD4 T cells to Th1 cells and Th17 cells and restricted the intracellular growth of . Furthermore, these DCs upregulated the expression of CCR7 and exhibited enhanced migratory capabilities. The discrete impact of Acr1 on DCs is mediated through a mechanism involving STAT-1, SOCS-3, ERK, TLR-4, and NF-κB signaling pathways. This study reveals the unprecedented role of Acr1 in distinctly modulating the function of DCs at different stages of maturation.
它有助于在宿主体内处于休眠状态。在潜伏期间会抑制其大部分代谢机制，但会上调潜伏期相关蛋白α-晶状体蛋白（Acr1）的表达。因此，了解在整个休眠过程中如何利用Acr1调节宿主免疫至关重要。本研究表明，Acr1对树突状细胞（DCs）的成熟前和成熟后阶段表现出不同的作用。在当前研究中，我们证明骨髓细胞在分化为DCs（AcrDC）时早期接触Acr1会导致其成熟受损。相反，当成熟后（AcrDC）暴露于Acr1时，DCs的活性、TNF-α、IL-12、IL-6的分泌以及T细胞的激活会增强。此外，AcrDC促进了初始CD4 T细胞向Th1细胞和Th17细胞的极化，并限制了其在细胞内的生长。此外，这些DCs上调了CCR7的表达并表现出增强的迁移能力。Acr1对DCs的不同影响是通过涉及STAT-1、SOCS-3、ERK、TLR-4和NF-κB信号通路的机制介导的。本研究揭示了Acr1在不同成熟阶段对DCs功能进行独特调节方面前所未有的作用。
