Gut-homing Δ42PD1+Vδ2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection.
Allen Ka Loon CheungHau-Yee KwokYiru HuangMin ChenYufei MoXilin WuKa-Shing LamHoi-Kuan KongTerrence Chi-Kwong LauJingying ZhouJingjing LiLin ChengBoon Kiat LeeQiaoli PengXiaofan LuMinghui AnHui WangHong ShangBoping ZhouHao WuAimin XuKwok-Yung YuenZhiwei ChenPublished in: Nature microbiology (2017)
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.
Keyphrases
- toll like receptor
- induced apoptosis
- immune response
- antiretroviral therapy
- end stage renal disease
- liver failure
- inflammatory response
- cell cycle arrest
- oxidative stress
- respiratory failure
- newly diagnosed
- binding protein
- hiv infected
- chronic kidney disease
- prognostic factors
- human immunodeficiency virus
- hiv positive
- peritoneal dialysis
- hepatitis c virus
- poor prognosis
- nuclear factor
- hiv aids
- fatty acid
- type diabetes
- cell death
- hiv testing
- aortic dissection
- bone marrow
- stem cells
- signaling pathway
- dendritic cells
- men who have sex with men
- south africa
- metabolic syndrome
- hepatitis b virus
- diabetic rats
- mechanical ventilation
- stress induced