Gut-homing Δ42PD1+Vδ2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Allen Ka Loon Cheung
  • Hau-Yee Kwok
  • Yiru Huang
  • Min Chen
  • Yufei Mo
  • Xilin Wu
  • Ka-Shing Lam
  • Jingying Zhou
  • Jingjing Li
  • Lin Cheng
  • Boon Kiat Lee
  • Qiaoli Peng
  • Xiaofan Lu
  • Minghui An
  • Hui Wang
  • Hong Shang
  • Boping Zhou
  • Hao Wu
  • Aimin Xu
  • Kwok-Yung Yuen
  • Zhiwei Chen

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)1389-1402
Journal / PublicationNature Microbiology
Volume2
Issue number10
Online published14 Aug 2017
Publication statusPublished - Oct 2017

Abstract

The innate immune cells underlying mucosal inflammatory responses and damage during acute HIV-1 infection remain incompletely understood. Here, we report a Vδ2 subset of gut-homing γδ T cells with significantly upregulated Δ42PD1 (a PD1 isoform) in acute (~20%) HIV-1 patients compared to chronic HIV-1 patients (~11%) and healthy controls (~2%). The frequency of Δ42PD1+Vδ2 cells correlates positively with plasma levels of pro-inflammatory cytokines and fatty-acid-binding protein before detectable lipopolysaccharide in acute patients. The expression of Δ42PD1 can be induced by in vitro HIV-1 infection and is accompanied by high co-expression of gut-homing receptors CCR9/CD103. To investigate the role of Δ42PD1+Vδ2 cells in vivo, they were adoptively transferred into autologous humanized mice, resulting in small intestinal inflammatory damage, probably due to the interaction of Δ42PD1 with its cognate receptor Toll-like receptor 4 (TLR4). In addition, blockade of Δ42PD1 or TLR4 successfully reduced the cytokine effect induced by Δ42PD1+Vδ2 cells in vitro, as well as the mucosal pathological effect in humanized mice. Our findings have therefore uncovered a Δ42PD1–TLR4 pathway exhibited by virus-induced gut-homing Vδ2 cells that may contribute to innate immune activation and intestinal pathogenesis during acute HIV-1 infection. Δ42PD1+Vδ2 cells may serve as a target for the investigation of diseases with mucosal inflammation.

Research Area(s)

  • HIV infections, Inflammatory diseases, Innate immunity, Viral host response

Citation Format(s)

Gut-homing Δ42PD1+Vδ2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection. / Cheung, Allen Ka Loon; Kwok, Hau-Yee; Huang, Yiru; Chen, Min; Mo, Yufei; Wu, Xilin; Lam, Ka-Shing; Kong, Hoi-Kuan; Lau, Terrence Chi Kong; Zhou, Jingying; Li, Jingjing; Cheng, Lin; Kiat Lee, Boon; Peng, Qiaoli; Lu, Xiaofan; An, Minghui; Wang, Hui; Shang, Hong; Zhou, Boping; Wu, Hao; Xu, Aimin; Yuen, Kwok-Yung; Chen, Zhiwei.

In: Nature Microbiology, Vol. 2, No. 10, 10.2017, p. 1389-1402.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal