HIV-1-induced cytokines deplete homeostatic innate lymphoid cells and expand TCF7-dependent memory NK cells.
Yetao WangLawrence LifshitzKyle J GellatlyCarol L VintonKathleen Busman-SahaySean McCauleyPranitha VangalaKyusik KimAlan DerrSmita JaiswalAlper KucukuralPatrick McDonelPeter W HuntThomas GreenoughJeanMarie HoughtonMa SomsoukJacob D EstesJason M BrenchleyManuel GarberSteven G DeeksJeremy LubanPublished in: Nature immunology (2020)
Human immunodeficiency virus 1 (HIV-1) infection is associated with heightened inflammation and excess risk of cardiovascular disease, cancer and other complications. These pathologies persist despite antiretroviral therapy. In two independent cohorts, we found that innate lymphoid cells (ILCs) were depleted in the blood and gut of people with HIV-1, even with effective antiretroviral therapy. ILC depletion was associated with neutrophil infiltration of the gut lamina propria, type 1 interferon activation, increased microbial translocation and natural killer (NK) cell skewing towards an inflammatory state, with chromatin structure and phenotype typical of WNT transcription factor TCF7-dependent memory T cells. Cytokines that are elevated during acute HIV-1 infection reproduced the ILC and NK cell abnormalities ex vivo. These results show that inflammatory cytokines associated with HIV-1 infection irreversibly disrupt ILCs. This results in loss of gut epithelial integrity, microbial translocation and memory NK cells with heightened inflammatory potential, and explains the chronic inflammation in people with HIV-1.
Keyphrases
- nk cells
- antiretroviral therapy
- human immunodeficiency virus
- hiv infected
- hiv positive
- hiv aids
- hiv infected patients
- oxidative stress
- induced apoptosis
- transcription factor
- cardiovascular disease
- cell cycle arrest
- working memory
- dna damage
- drug induced
- microbial community
- type diabetes
- stem cells
- endoplasmic reticulum stress
- diabetic rats
- squamous cell carcinoma
- signaling pathway
- endothelial cells
- risk factors
- cell proliferation
- liver failure
- immune response
- risk assessment
- coronary artery disease
- hiv testing
- men who have sex with men
- respiratory failure
- climate change
- papillary thyroid
- young adults
- dna methylation
- acute respiratory distress syndrome
- metabolic syndrome
- dna binding
- south africa