Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Manauli, Punjab, India.
Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Manauli, Punjab, India
Infect Immun. 2019 Apr 23;87(5). doi: 10.1128/IAI.00809-18. Print 2019 Mar.
is a human pathogen, and it is a major cause of severe gastroenteritis in coastal areas. OmpU is one of the major outer membrane porins of Host-immunomodulatory effects of OmpU (VpOmpU) have not been elucidated yet. In this study, in an effort towards characterizing the effect of VpOmpU on innate immune responses of the host, we observed that VpOmpU is recognized by the Toll-like receptor 1/2 (TLR1/2) heterodimer in THP-1 monocytes but by both TLR1/2 and TLR2/6 heterodimers in RAW 264.7 macrophages. To the best of our knowledge, this is the first report of a natural pathogen-associated molecular pattern (PAMP) recognized by both TLR1/2 and TLR2/6 heterodimers; so far, mainly the synthetic ligand PamCSK4 has been known to be recognized by both the TLR1/2 and TLR2/6 heterodimers. We also have shown that VpOmpU can activate monocytes and macrophages, leading to the generation of proinflammatory responses as indicated by tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and NO production in macrophages and TNF-α and IL-6 production in monocytes. VpOmpU-mediated proinflammatory responses involve MyD88-IRAK-1 leading to the activation of mitogen-activated protein (MAP) kinases (p38 and Jun N-terminal protein kinase [JNK]) and transcription factors NF-κB and AP-1. Further, we have shown that for the activation of macrophages leading to the proinflammatory responses, the TLR2/6 heterodimer is preferred over the TLR1/2 heterodimer. We have also shown that MAP kinase activation is TLR2 mediated.
是一种人类病原体，也是沿海地区严重胃肠炎的主要病因。OmpU 是 的主要外膜孔蛋白之一。 OmpU（VpOmpU）的宿主免疫调节作用尚未阐明。在这项研究中，为了研究 VpOmpU 对宿主固有免疫反应的影响，我们观察到 VpOmpU 被 THP-1 单核细胞中的 Toll 样受体 1/2（TLR1/2）异二聚体识别，但被 RAW 264.7 巨噬细胞中的 TLR1/2 和 TLR2/6 异二聚体识别。据我们所知，这是第一个被 TLR1/2 和 TLR2/6 异二聚体识别的天然病原体相关分子模式（PAMP）的报道；到目前为止，主要是合成配体 PamCSK4 被 TLR1/2 和 TLR2/6 异二聚体识别。我们还表明，VpOmpU 可以激活单核细胞和巨噬细胞，导致产生促炎反应，如巨噬细胞中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和一氧化氮（NO）的产生以及单核细胞中 TNF-α 和 IL-6 的产生。VpOmpU 介导的促炎反应涉及 MyD88-IRAK-1，导致丝裂原激活蛋白（MAP）激酶（p38 和 Jun N-末端蛋白激酶 [JNK]）和转录因子 NF-κB 和 AP-1 的激活。此外，我们表明，对于导致促炎反应的巨噬细胞激活，TLR2/6 异二聚体优先于 TLR1/2 异二聚体。我们还表明，MAP 激酶的激活是 TLR2 介导的。
