bims-maitce 2026-11-08 papers

Issue of 2026–11–08
two papers selected by
Andy E. Hogan, Maynooth University

PLoS Pathog. 2026 Nov;22(11): e1014715

Modulation of riboflavin biosynthesis enzymes in non-typhoidal Salmonella isolates differentially impacts human MAIT cell activation.

Leia Vainman, Corinna A Kulicke, Nurudeen Oketade, Noa Bossel Ben-Moshe, Camilla Ciolli-Mattioli, Aryeh Solomon, Jay C D Hinton, Karen M Dobos, David M Lewinsohn, Shelly Hen-Avivi, Roi Avraham.

Invasive non-typhoidal Salmonella (iNTS) sequence type 313 (ST313) isolates have emerged in sub-Saharan Africa, with a high incidence of multidrug resistance, enhanced intracellular persistence, increased dissemination and immune evasion. ST313 isolate D23580 was shown to avoid activation of mucosal-associated invariant T (MAIT) cells compared with a genetically similar, non-invasive Salmonella Typhimurium (S.Tm) 4/74 strain, but the mechanism remains unclear. Here, we studied immune responses to infection with typhoidal strains and ST313 isolates using comparative transcriptomic profiling of human peripheral blood mononuclear cells (PBMCs). MAIT cells responded to typhoidal strains but not to D23580. To uncover underlying mechanisms, we engineered an inducible CRISPRi system targeting riboflavin biosynthesis enzymes (rib), which process MAIT ligands, in D23580 and 4/74 strains. Several rib hypomorphs exhibited prolonged lag time in minimal media, which was more pronounced in D23580 than in 4/74. In PBMC infection, knockdown of lumazine synthase (RibH) and riboflavin synthase (RibE) resulted in contrasting MAIT cell activation phenotypes. RibH knockdown restored MAIT cell activation in D23580 but did not affect activation in 4/74. Conversely, RibE knockdown diminished MAIT cell activation by 4/74 but had no impact on MAIT cell activation by D23580. Metabolomic analysis revealed accumulation of the biosynthetic intermediate DMRL in RibE knockdown and a differential impact on riboflavin biosynthesis end products between D23580 and 4/74 RibH knockdown, suggesting altered pathway flux between the strains. Our results indicate RibH and RibE as pivotal nodes for strain-specific MAIT-activation during Salmonella infection of human PBMCs, illustrating teir central role in the complex interplay between bacterial metabolism and host immunity.

DOI: https://doi.org/10.1371/journal.ppat.1014715

Front Immunol. 2026 ;17 1982931

Lymphocyte trajectories after liver transplantation: immune mechanisms, clinical associations, and research priorities.

Jiajun Gao, Zhaoyun Shi, Xuantong Jin, Zhiqi Jiao, Zhenyu Xu, Genhua Ye, Yuhui Wang, Fangliang Guo, Lianbo Yang, Zhenming Gao.

Liver transplantation (LT) is an established treatment for end-stage liver disease, yet rejection, infection, biliary injury, post-transplant lymphoproliferative disorder, and tumour recurrence continue to limit outcomes. Post-transplant immune states reflect alloantigen exposure, immunosuppression, microbial or viral stimulation, and inflammation within the graft. This Review examines longitudinal changes in CD8+ and CD4+ T cells, regulatory and follicular T-cell populations, B cells, natural killer cells, mucosal-associated invariant T cells, and γδ T cells after LT. The most direct evidence concerns acute cellular rejection, in which transient effector activation, T helper 1/interferon-γ responses, multicellular T-cell-B-cell signatures, and graft-local clonal programmes have been described. Early infection has been linked to inhibitory-receptor coexpression and impaired protective function, although treatment exposure, viral history, and phenotype definitions affect interpretation. An increase in circulating regulatory T cells alone does not establish operational tolerance; donor specificity, suppressive stability, and intrahepatic localisation are also required. Evidence relating lymphocyte subsets to biliary, vascular, metabolic, and oncological outcomes is less direct and often comes from experimental or non-transplant studies. Meaningful interpretation requires attention to sampling time, anatomical compartment, cellular function, and treatment exposure. Serial blood phenotyping may be combined with functional assays, soluble immune-mediator or protein signatures, graft histology, immune-receptor repertoires, and selected single-cell or spatial analyses. This approach defines research priorities, not a validated score or treatment algorithm. Clinical use will require standardised sampling, prespecified outcomes, externally validated thresholds, and prospective strategy trials that assess both benefit and harm.

Keywords: immune monitoring; immune tolerance; infection; liver transplantation; longitudinal trajectories; lymphocyte subsets; rejection; tumour recurrence

DOI: https://doi.org/10.3389/fimmu.2026.1982931