Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection.
Kerri G LalDohoon KimMargaret C CostanzoMatthew CreeganEdwin LeeansyahJoana DiasDominic Paquin-ProulxLeigh Anne EllerAlexandra SchuetzYuwadee Phuang-NgernShelly J KrebsBonnie M SlikeHannah KibuukaLucas MagangaSorachai NitayaphanJosphat KosgeiCarlo SacdalanJintanat AnanworanichDiane L BoltonNelson L MichaelBarbara L ShacklettMerlin L RobbMichael A EllerJohan K SandbergPublished in: Nature communications (2020)
Mucosa-associated invariant T (MAIT) cell loss in chronic HIV-1 infection is a significant insult to antimicrobial immune defenses. Here we investigate the response of MAIT cells during acute HIV-1 infection utilizing the RV217 cohort with paired longitudinal pre- and post-infection samples. MAIT cells are activated and expand in blood and mucosa coincident with peak HIV-1 viremia, in a manner associated with emerging microbial translocation. This is followed by a phase with elevated function as viral replication is controlled to a set-point level, and later by their functional decline at the onset of chronic infection. Interestingly, enhanced innate-like pathways and characteristics develop progressively in MAIT cells during infection, in parallel with TCR repertoire alterations. These findings delineate the dynamic MAIT cell response to acute HIV-1 infection, and show how the MAIT compartment initially responds and expands with enhanced function, followed by progressive reprogramming away from TCR-dependent antibacterial responses towards innate-like functionality.
Keyphrases
- induced apoptosis
- antiretroviral therapy
- cell cycle arrest
- liver failure
- immune response
- single cell
- cell therapy
- drug induced
- hiv infected
- respiratory failure
- mycobacterium tuberculosis
- human immunodeficiency virus
- hiv positive
- endoplasmic reticulum stress
- aortic dissection
- oxidative stress
- sars cov
- signaling pathway
- stem cells
- staphylococcus aureus
- intensive care unit
- pi k akt
- cross sectional
- south africa
- acute respiratory distress syndrome
- men who have sex with men