bims-maitce 2024-03-10 papers

Issue of 2024–03–10
three papers selected by
Andy E. Hogan, Maynooth University

Clin Exp Immunol. 2024 Mar 02. pii: uxae019. [Epub ahead of print]

Conventional and unconventional T cell responses contribute to the prediction of clinical outcome and causative bacterial pathogen in sepsis patients.

Ross J Burton, Loïc Raffray, Linda M Moet, Simone M Cuff, Daniel A White, Sarah E Baker, Bernhard Moser, Valerie B O'Donnell, Peter Ghazal, Matt P Morgan, Andreas Artemiou, Matthias Eberl.

Sepsis is characterised by a dysfunctional host response to infection culminating in life-threatening organ failure that requires complex patient management and rapid intervention. Timely diagnosis of the underlying cause of sepsis is crucial, and identifying those at risk of complications and death is imperative for triaging treatment and resource allocation. Here, we explored the potential of explainable machine learning models to predict mortality and causative pathogen in sepsis patients. By using a modelling pipeline employing multiple feature selection algorithms, we demonstrate the feasibility to identify integrative patterns from clinical parameters, plasma biomarkers and extensive phenotyping of blood immune cells. Whilst no single variable had sufficient predictive power, models that combined five and more features showed a macro area under the curve (AUC) of 0.85 to predict 90 day mortality after sepsis diagnosis, and a macro AUC of 0.86 to discriminate between Gram-positive and Gram-negative bacterial infections. Parameters associated with the cellular immune response contributed the most to models predictive of 90 day mortality, most notably, the proportion of T cells among PBMCs, together with expression of CXCR3 by CD4+ T cells and CD25 by mucosal-associated invariant T (MAIT) cells. Frequencies of Vδ2+ γδ T cells had the most profound impact on the prediction of Gram-negative infections, alongside other T cell-related variables and total neutrophil count. Overall, our findings highlight the added value of measuring the proportion and activation patterns of conventional and unconventional T cells in the blood of sepsis patients in combination with other immunological, biochemical and clinical parameters.

Keywords: Cytokines; Endotoxin Shock; Inflammation; Sepsis; Unconventional T Cells

DOI: https://doi.org/10.1093/cei/uxae019

Front Immunol. 2024 ;15 1341180

Functions of mucosal associated invariant T cells in eye diseases.

Chihiro Fukui, Satoshi Yamana, Yanqi Xue, Mariko Shirane, Hiroki Tsutsui, Kenichiro Asahara, Keiko Yoshitomi, Takako Ito, Tantri Lestari, Eiichi Hasegawa, Nobuyo Yawata, Atsunobu Takeda, Koh-Hei Sonoda, Kensuke Shibata.

Mucosal-associated invariant T (MAIT) cells are a unique subset of T cells that recognizes metabolites derived from the vitamin B2 biosynthetic pathway. Since the identification of cognate antigens for MAIT cells, knowledge of the functions of MAIT cells in cancer, autoimmunity, and infectious diseases has been rapidly expanding. Recently, MAIT cells have been found to contribute to visual protection against autoimmunity in the eye. The protective functions of MAIT cells are induced by T-cell receptor (TCR)-mediated activation. However, the underlying mechanisms remain unclear. Thus, this mini-review aims to discuss our findings and the complexity of MAIT cell-mediated immune regulation in the eye.

Keywords: T cells; autoimmune disease; eye; immunotherapy; metabolite

DOI: https://doi.org/10.3389/fimmu.2024.1341180

Pigment Cell Melanoma Res. 2024 Mar 04.

Topical antibiotics limit depigmentation in a mouse model of vitiligo.

Ahmed Ahmed Touni, Rachel Sohn, Cormac Cosgrove, Rohan S Shivde, Emilia R Dellacecca, Rasha T A Abdel-Aziz, Kettil Cedercreutz, Stefan J Green, Hossam Abdel-Wahab, I Caroline Le Poole.

Oral neomycin administration impacts the gut microbiome and delays vitiligo development in mice, and topical antibiotics may likewise allow the microbiome to preserve skin health and delay depigmentation. Here, we examined the effects of 6-week topical antibiotic treatment on vitiligo-prone pmel-1 mice. Bacitracin, Neosporin, or Vaseline were applied to one denuded flank, while the contralateral flank was treated with Vaseline in all mice. Ventral depigmentation was quantified weekly. We found that topical Neosporin treatment significantly reduced depigmentation and exhibited effects beyond the treated area, while Bacitracin ointment had no effect. Stool samples collected from four representative mice/group during treatment revealed that Neosporin treatment aligned with reduced abundance of the Alistipes genus in the gut, while relevant changes to the skin microbiome at end point were less apparent. Either antibiotic treatment led to reduced expression of MR1, potentially limiting mucosal-associated invariant T-cell activation, while Neosporin-treated skin selectively revealed significantly reduced CD8+ T-cell abundance. The latter finding aligned with reduced expression of multiple inflammatory markers and markedly increased regulatory T-cell density. Our studies on favorable skin and oral antibiotic treatment share the neomycin compound, and in either case, microbial changes were most apparent in stool samples. Taken together, neomycin-containing antibiotic applications can mediate skin Treg infiltration to limit vitiligo development. Our study highlights the therapeutic potential of short-term antibiotic applications to limit depigmentation vitiligo.

Keywords: T-cell subsets; antibiotics; depigmentation; microbiome; vitiligo

DOI: https://doi.org/10.1111/pcmr.13164