bims-maitce 2026-08-30 papers

Issue of 2026–08–30
four papers selected by
Andy E. Hogan, Maynooth University

Front Immunol. 2026 ;17 1882545

Phenotypic characterization of mucosal-associated invariant T cells in visceral leishmaniasis and HIV co-infection.

Victoria Hellena Silva Pereira, Gustavo Augusto Fonseca Nogueira, Luana Borges-Fernandes, Silvia Hees de Carvalho, Adelina Machado de Carvalho Nogueira, Argus Leão Araújo, Joaquim Pedro Brito-de-Sousa, Juliana Assunção Rodrigues, João Paulo Resende Magalhães Toledo, Vanessa Caroline Randi Magalhães, Jairo Campos de Carvalho, Livia Fulgencio da Cunha, Jordana Grazziela Alves Coelho-Dos-Reis, Andréa Teixeira-Carvalho, Olindo Assis Martins-Filho, Gabriel Macedo Costa Guimarães, Vanessa Peruhype-Magalhães.

Introduction: Mucosal-associated invariant T (MAIT) cells are unconventional T lymphocytes with innate-like antimicrobial responsiveness. Despite their recognized role in bacterial and viral infections, their involvement in protozoal diseases, particularly visceral leishmaniasis (VL) and HIV co-infection, remains poorly understood.
Methods: A cross-sectional study evaluated the immunophenotypic profile of circulating MAIT cells in visceral leishmaniasis patients (VL, n = 8), VL-HIV co-infection patients (VL-HIV, n = 10), VL-HIV coinfected patients under liposomal amphotericin B prophylactic treatment (VL-HIV(T), n = 9), and reference groups comprising HIV-mono-infected (HIV, n = 11) and non-infected (NI, n = 11) individuals. Multiparameter flow cytometry assessed MAIT cell frequency, subset distribution (CD4+, CD8+ and CD4-CD8-), and the expression of activation, costimulatory, cytotoxic, exhaustion and memory markers. Integrative correlation network analysis was performed to evaluate immunological interactions among MAIT cell markers.
Results: MAIT cell frequencies were significantly reduced in VL and VL-HIV, predominantly affecting the CD8+ subset. Fold-change analyses demonstrated increased activation and cytotoxicity signatures in VL and VL-HIV patients, with marked upregulation of CD69, CD38, NKG2D, and CD107A, concomitant with increased expression of inhibitory receptors (PD-1, TIM-3, LAG-3), particularly in CD8+ and CD4-CD8- MAIT cells. In contrast, VL-HIV(T) patients exhibited a decrease in this hyperactivated/exhausted phenotype and partial restoration of central memory-associated features, suggesting immune rebalancing under treatment. Integrative correlation network analysis revealed marked differences of MAIT cell immunological interactions. VL and VL-HIV groups displayed reduced network density, decreased selective axis connectivity, and fragmentation of interactions among activation, cytotoxicity, and memory nodes, consistent with immune disorganization. Conversely, treated VL-HIV(T) patients exhibited increased connectivity and re-establishment of coordinated interactions between functional markers, indicating partial re-establishment of the MAIT cell immunological network architecture.
Discussion: Together, VL and VL-HIV co-infection are associated with quantitative depletion and qualitative dysregulation of circulating MAIT cells, characterized by concurrent hyperactivation and exhaustion, coupled with immunological network fragmentation, while liposomal amphotericin B treatment appears to promote partial immunological reorganization.

Keywords: HIV co-infection; MAIT cells; flow cytometry; immune exhaustion; visceral leishmaniasis

DOI: https://doi.org/10.3389/fimmu.2026.1882545

Front Immunol. 2026 ;17 1896626

Unconventional guardians of the brain: MAIT cells as emerging players in glioblastoma immunity.

Eleanor M Eddy, Timothy Patton, Alexander D Barrow, Alexandra J Corbett.

Glioblastomas (GBM) are an aggressive form of brain cancer with no curative treatment options. While T cell therapies have demonstrated substantial success in combatting blood cancers, their application for solid tumours, including GBM, is hampered by the immunosuppressive tumour microenvironment and scarcity of tumour antigen-specific targets. There is an urgent need to better understand the immune response to GBM to enable the development of new therapeutic approaches. Recently, a resident population of mucosal-associated invariant T (MAIT) cells in the brain has been described, which may perform critical immune surveillance functions. Recent research also suggests that MAIT cells play diverse roles in anti-tumour immunity, and there is much interest in exploring the potential of MAIT cells in immune therapy by harnessing their cytotoxic capacity and tissue homing properties. However, findings on the role of MAIT cells in cancer are conflicting, while many basic questions regarding MAIT-tumour cell interactions remain. Here we review the challenges for GBM treatment, as well as the potential of unconventional T cells in cancer immunotherapy, with a focus on MAIT cells, their potential role in cancer, and their suitability as novel therapeutic targets in solid tumours such as GBM.

Keywords: GBM; MAIT cells; brain; glioblastoma; immune therapy

DOI: https://doi.org/10.3389/fimmu.2026.1896626

Front Immunol. 2026 ;17 1931069

Multifaceted mechanisms of unconventional T cells in ischemia-reperfusion injury.

Jiajun Li, Peizhe Lin, Menghan Yuan, Yulin Wang, Hongyuan Liu, Ruo Jia, Jinghan Fan, Li Liang, Pingping Han, Qiujun Guo, Yuzhou He.

Ischemia-reperfusion injury (IRI) constitutes a common pathological basis for organ dysfunction across various critical clinical conditions, including ischemic stroke, myocardial infarction, and organ transplantation. This review focuses on the functions of unconventional T cells in IRI in the brain, liver, kidneys, heart, and mucosal barrier organs, highlighting their diverse regulatory mechanisms in various tissue injury patterns. It also examines the dual functions of these cells in IRI: instead of solely acting as consistent pro-inflammatory effectors, they demonstrate a context-dependent immunomodulatory profile influenced by the organ microenvironment and disease stage, capable of promoting inflammatory damage and facilitating anti-inflammatory repair. Their behavior is shaped by a common injury response program that integrates local antigen cues, the cytokine milieu, metabolic checkpoints, and signals from the repair stage. Expounding on the spatiotemporal heterogeneity, functional plasticity, and regulatory networks of unconventional T cells in IRI will enhance our understanding of the immunopathological mechanisms. It also offers a theoretical basis and potential targets for formulating precision immunomodulatory strategies tailored to specific time windows and cell subsets.

Keywords: MAIT cells; NKT cells; ischemia-reperfusion injury; sterile inflammation; unconventional T cells; γδ T cells

DOI: https://doi.org/10.3389/fimmu.2026.1931069

Front Immunol. 2026 ;17 1864805

The gut-liver-immune axis: structural basis, cellular architecture, molecular mediators, and disease-specific manifestations.

Sang Jun Yoon, Jung A Eom, Ki Tae Suk.

The gut and liver form an anatomical and functional unit linked by the portal circulation, the biliary tract, lymphatic drainage, and neuroimmune pathways. In recent years, the classical gut-liver axis has expanded from a predominantly microbial and metabolic concept into a broader framework in which immune cells are viewed as central integrators of inter-organ signaling. In health, balanced microbial sensing, intact mucosal and vascular barriers, regulated bile acid signaling, and specialized tissue-resident immune programs preserve tolerance at both intestinal and hepatic interfaces. In disease, dysbiosis, barrier failure, altered bile acid pools, endogenous hepatotoxic metabolites, and aberrant immune-cell trafficking remodel the hepatic immune niche and drive steatohepatitis, alcohol-associated liver injury, cholangiopathy, cirrhosis, acute decompensation, and hepatocellular carcinoma. This review reframes the gut-liver axis as a gut-liver-immune axis and synthesizes current evidence on its structural basis, cellular architecture, molecular mediators, and disease-specific manifestations. We discuss the roles of macrophages, dendritic cells, neutrophils, innate-like T cells, natural killer cells, and adaptive T-cell subsets in translating gut-derived signals into hepatic inflammation, tissue repair, fibrosis, or tumor surveillance. We also highlight the bidirectional role of the liver in shaping intestinal immunity, particularly through bile acids and hepatobiliary-derived mediators. Finally, we examine current therapeutic strategies targeting the microbiota, mucosal barrier, bile acid signaling, and immune-cell trafficking, and we outline major conceptual and translational gaps that should guide the next generation of mechanistic and clinical studies.

Keywords: MAIT cells; Treg/Th17 balance; bile acids; gut-liver axis; gut-liver-immune axis; intestinal barrier; liver disease; macrophages

DOI: https://doi.org/10.3389/fimmu.2026.1864805