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Divergent metabolic programs control two populations of MAIT cells that protect the lung

ABSTRACT: Although mucosal associated invariant T (MAIT) cells provide rapid, innate-like responses, they are not pre-set and memory-like responses have been described for MAIT cells following infections. The importance of metabolism for controlling these responses, however, is unknown. Following pulmonary immunization with a Salmonella vaccine strain, mouse MAIT cells expanded as separate CD127-Klrg1+ and CD127+Klrg1- antigen-adapted populations that differed for their transcriptome, function and localization in lung tissue. These populations remained altered from steady-state for months as stable, separate MAIT cell lineages with enhanced effector programs and divergent metabolism. CD127+ MAIT cells engaged in an energetic, mitochondrial metabolic program, which was critical for their maintenance and IL-17A synthesis. This program was supported by high fatty acid uptake and mitochondrial oxidation and relied on highly polarized mitochondria and autophagy. After vaccination, CD127+ MAIT cells protected mice against Streptococcus pneumoniae infection. In contrast, Klrg1+ MAIT cells had dormant, but ready-to-respond mitochondria and depended instead on Hif1a-driven glycolysis. They responded vigorously to cytokines and participated in protection from influenza virus. These metabolic dependencies may enable tuning of memory-like MAIT cell responses for vaccinations and immunotherapies.

ORGANISM(S): Mus musculus

PROVIDER: GSE226524 | GEO | 2023/03/29

REPOSITORIES: GEO

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IL-27 produced during acute malaria infection regulates Plasmodium-specific memory CD4+ T cells

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2023-10-19 | GSE225556 | GEO

A conserved population of MHC II-restricted, innate-like, commensal-reactive T cells in the gut of humans and mice

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2021-04-27 | GSE173424 | GEO

Expression data from LCMV-infected P14 and Akt transgenic P14 CD8 T cells

Project description:The PI3K/Akt signaling pathway impacts various aspects of CD8 T cell homeostasis, such as effect versus memory cell differentiation, during viral infection. We used microarrays to determine which downstream molecules were affected and what other signaling pathways were interconnected with the Akt pathway by constitutive activation of Akt in LCMV-infected CD8 T cells. Splenocytes from naive P14/WT or P14/Akt mice were stained with anti-CD8 and anti-Ly5.1, and CD8 T cells were sorted using a FACSAria II instrument. Purified Ly5.1+ CD8 T cells from P14/WT or P14/Akt mice were transferred into B6 mice, which were subsequently infected with LCMV Armstrong. At day 8 post infection, splenocytes were stained with anti-CD8, anti-Ly5.1, anti-KLRG1, and anti-CD127. Following staining, short-lived effector cells (SLECs) and memory precursor effector cells (MPECs) were sorted using the FACSAria II instrument; the purity of the sorted cells was >95%. A total of 5 samples were analyzed, including WT naive, WT SLEC, WT MPEC, Akt naive and Akt SLEC.

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