bims-maitce 2025-07-27 papers

Issue of 2025–07–27
four papers selected by
Andy E. Hogan, Maynooth University

Alzheimers Dement. 2025 Jul;21(7): e70493

The MR1/MAIT cell axis impacts the gut-brain axis through both cognition and microbial community structure in 5XFAD mice.

Season K Wyatt-Johnson, Jay M Desai, Autumn Wireman, Peter Eipers, Casey Morrow, Jay Vornhagen, Randy R Brutkiewicz.

INTRODUCTION: Mucosal-associated invariant T (MAIT) cells recognize microbial antigens presented by major histocompatibility complex class I-like molecule (MR1) and are elevated in Alzheimer's disease (AD) model mouse brains; MAIT cell-deficient AD mice have reduced brain pathology, supporting the importance of the gut-brain axis in AD. How the MR1/MAIT cell axis impacts cognition and the microbiome remains unknown.
METHODS: Novel object recognition/placement, Y-maze, and Barnes maze were used to determine memory changes in wild-type (WT), MR1 KO, 5XFAD, and 5XFAD/MR1 KO mice. Fecal samples were analyzed using 16S rRNA gene amplicon sequencing.
RESULTS: 5XFAD/MR1KO mice did not display the cognitive deficits observed in 5XFAD. There were relative abundance differences in the fecal microbiota between 5XFAD and 5XFAD/MR1 KO mice, and male 5XFAD/MR1 KO mice had increased microbiome alpha diversity compared to 5XFAD mice.
DISCUSSION: Our data suggest that the MR1/MAIT cell axis negatively affects cognition and impacts gut microbiome diversity. These results further support a detrimental role for the MR1/MAIT cell axis in AD.
HIGHLIGHTS: 5XFAD mice lacking major histocompatibility complex, class I-related (MR1) and mucosal-associated invariant T (MAIT) cells had no deficits in recognition memory. Compared to 5XFAD, there was improved learning in the Barnes maze by female 5XFAD/MR1 knock-out (KO) mice. There was an increased abundance of Campylobacterota in male 5XFAD/MR1 KO versus 5XFAD mice. Six of nine linear discriminant analysis effect size-identified distinguishing features were higher in 5XFAD/MR1 KO mice.

Keywords: 5XFAD; Mucosal‐associated invariant T cells; gut–brain axis; innate immunity; major histocompatibility complex class I‐like molecule; memory; sex differences

DOI: https://doi.org/10.1002/alz.70493

J Immunol Res. 2025 ;2025 1203141

Poxvirus Vectors Activate Human NK and MAIT Cells in a Type I Interferon, IL-18, and Monocyte-Dependent Manner.

Kombo F N'guessan, Zhanna Shubin, Kawthar Machmach, Johan K Sandberg, Julie A Ake, Sandhya Vasan, Michael A Eller, Dominic Paquin-Proulx.

Recombinant poxviruses have been extensively studied as vaccine vectors, yet the specific mechanisms by which they engage the immune system remain incompletely understood. ALVAC is a poxviral vector that was a component of the HIV vaccine used in the Thai RV144 trial, showing modest efficacy in reducing HIV acquisition. Here, we show that in vitro ALVAC-HIV infection of peripheral blood mononuclear cells (PBMCs) activates natural killer (NK) and mucosal-associated invariant T (MAIT) cells. This activation was partially dependent on monocytes, cGAS sensing, and production of IL-18 and type I IFN. Furthermore, ALVAC-HIV-mediated activation of NK and MAIT cells contributed to the activation of B cells. Modified vaccinia Ankara (MVA), another poxviral vector used for prevention of smallpox and mpox, similarly activated NK and MAIT cells. Overall, this suggests a conserved mechanism by which NK and MAIT cells could contribute to the immunogenicity of poxviral vectors.

Keywords: ALVAC; MAIT cells; MVA; NK cells; poxvirus; viral vector

DOI: https://doi.org/10.1155/jimr/1203141

Cytometry A. 2025 Jul 22.

OMIP-116: A 39-Color Full Spectrum Flow Cytometric Panel to Deeply Characterize Human Thymopoiesis.

Simone Balin, Paolo Marzano, Daniele Manganaro, Anna Villa, Paolo Andrea Zucali, Domenico Mavilio, Silvia Della Bella.

We report the development of a 39-color (43-parameter) full spectrum flow cytometry panel designed and optimized to deeply characterize the intrathymic development of human conventional and unconventional T cells. The panel was designed using strategies dictated by best practices for full spectrum and multiparametric flow cytometry, and was validated using appropriate negative and positive controls. By including several markers that are variably expressed during T cell development, this panel allows the definition of T cell maturation stages and the investigation of possible deviation from normal thymopoiesis at unprecedented resolution, thus representing a valuable tool for understanding immune dysregulation associated with altered thymopoiesis, as occurring in immune deficiencies, thymic lesions, and immunosenescence. Notably, because most of the molecules targeted in this panel are also commonly used as activation markers or immune checkpoints on mature T cells, this 39-color panel can also be applied for a comprehensive profiling of peripheral T cells, particularly in those peripheral tissues where unconventional T cells, including Vδ1, Vδ2, and Vδ3 T cell subsets and MAIT cells, interact with αβ T cells to shape the local microenvironment.

DOI: https://doi.org/10.1002/cyto.a.24951

Front Immunol. 2025 ;16 1611976

Anti-HBV treatment partially restores the dysfunction of innate immune cells and unconventional T cells during chronic HBV infection.

Yiwen Shu, Sumeng Li, Yanqin Du, Xin Zheng.

Despite the successful implementation of prophylactic vaccines, hepatitis B virus (HBV) continues to affect over 350 million individuals globally. It remains a predominant etiology of end-stage liver pathologies, including liver cirrhosis and hepatocellular carcinoma (HCC). While nucleos(t)ide analog (NUC) therapies effectively suppress viral replication, functional cure is achieved in less than 1% of patients annually. Given that viral clearance fundamentally requires reconstitution of antiviral immunity, emerging therapeutic paradigms necessitate combinatorial strategies integrating direct-acting antiviral agents with immunomodulatory interventions. Substantial research efforts have been directed toward elucidating the immunological mechanisms underlying HBV persistence during chronic infection. This review systematically summarizes the functional impairment of innate immune populations and unconventional T cell subsets across distinct clinical phases of chronic HBV infection, and characterizes longitudinal immune reconstitution patterns following antiviral treatments. Our review identifies potential immunological biomarkers and provides a mechanistic framework for developing targeted immunotherapies to achieve durable HBV control.

Keywords: MAIT (mucosal-associated invariant T) cell; NKT (natural killer T) cell; antiviral treatment; dendritic cell (DC); hepatitis B virus; monocyte; natural killer (Nk) cell; γδT cell

DOI: https://doi.org/10.3389/fimmu.2025.1611976