NDV entry into dendritic cells through macropinocytosis and suppression of T lymphocyte proliferation

Tan, Lei and Zhang, Yuqiang and Qiao, Changtao and Yuan, Yanmei and Sun, Yingjie and Qiu, Xusheng and Meng, Chunchun and Song, Cuiping and Liao, Ying and Munir, Muhammad and Nair, Venugopal and Ding, Zhuang and Liu, Xiufan and Ding, Chan (2018) NDV entry into dendritic cells through macropinocytosis and suppression of T lymphocyte proliferation. Virology, 518. pp. 126-135. ISSN 0042-6822

Abstract

Newcastle disease virus (NDV) causes major economic losses in the poultry industry. Previous studies have shown that NDV utilizes different pathways to infect various cells, including dendritic cells (DCs). Here, we demonstrate that NDV gains entry into DCs mainly via macropinocytosis and clathrin-mediated endocytosis. The detection of cytokines interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12), interleukin-4 (IL-4) and interleukin-10 (IL-10) indicates that NDV significantly induces Th1 responses and lowers Th2 responses. Furthermore, NDV entry into DCs resulted in the upregulation of TNF-related apoptosis-inducing ligand (TRAIL) and cleaved caspase-3 proteins, which in turn activated the extrinsic apoptosis pathway and induced DCs apoptosis. Transwell® co-culture demonstrated that direct contact between live NDV-stimulated DCs and T cells, rather than heated-inactivated NDV, inhibited CD4+T cell proliferation. Taken together, these findings provide new insights into the mechanism underlying NDV infections, particularly in relation to antigen presentation cells and suppression of T cell proliferation.