Immunology

eLife Assessment

This important study shows that the Nora virus, a natural Drosophila pathogen that also persistently infects many laboratory fly stocks, infects intestinal stem cells (ISCs), leading to a shorter life span and increased sensitivity to intestinal infection with the bacterium Pseudomonas. The authors provide convincing data to support their conclusions. The paper provides new insights into virus-host interactions in the Drosophila gut and serves as a warning for scientists who use the fruit fly as a model to study gut physiology.

eLife Assessment

This useful study addresses the interesting question of how immune cells recognise infected erythrocytes in malaria. It proposes the parasite protein PfGBP-130 as an interaction partner of the human cell surface protein LFA 1, which could help explain how NK cells recognize infected erythrocytes. The conclusions are partially supported by pull-down and cell-based activation data. However, the overall evidence of direct interaction at the cell-cell interface and downstream effects is incomplete; stronger evidence is required to demonstrate surface exposure of PfGBP-130, as well as a direct role of this antigen in killing.

eLife Assessment

This study provides valuable findings regarding potential correlates of protection against the African swine fever virus. The evidence supporting the claims is solid, and the results are highly relevant to the field. Further analysis using larger number of animals and other virus strains will help validate the importance of these findings and assess the relevance of the immune parameters associated with protection. The work will be of broad interest to veterinary immunologists, and particularly those working on African swine fever.

eLife Assessment

This study presents compelling evidence supporting the therapeutic potential of trained immunity in Colitis. The study is important for the field of trained immunity and is a welcome addition to the focus issue on trained immunity.

eLife Assessment

This study provides a valuable contribution to the field of zebrafish immunology by demonstrating that the two TNF paralogs tnfa and tnfb show distinct cellular sources and temporal expression patterns during inflammation. These findings are potentially significant because they suggest regulatory divergence and functional specialization within the TNF signaling system in teleosts. While the evidence supporting differential expression is convincing, the work remains largely observational and would benefit from functional experiments and deeper mechanistic insight to determine whether these differences translate into distinct roles in inflammatory signaling. This work will be of interest to immunologists interested in inflammatory cytokine evolution and immune regulation in vertebrates.

eLife Assessment

This useful and interesting study provides evidence that EABR mRNA is at least as effective as standard S mRNA vaccines for SARS-CoV-2. The authors provide convincing justification for the conclusion that the inconsistent statistical significance for Omicron is likely due to immune imprinting or original antigenic sin. In this regard, the significance of the findings is stronger as it points to possible challenges for updated vaccine strategies in overcoming immune imprinting.

eLife Assessment

The study provides important mechanistic insight into the transcriptional control of γδT17 development, elegantly demonstrating how HEB and Id3 act sequentially and cooperatively to regulate γδT17 cell specification and maturation. The study provides compelling evidence that advances the understanding of E-Id protein dynamics in thymic T cell specification. The work is comprehensive, technically rigorous, and conceptually clear, and will be of interest to immunologists, developmental biologists, and those studying the molecular underpinnings of physiological outcomes.

eLife Assessment

This important study examines the role of TNF in modulating energy metabolism during parasite infection. The authors perform an elegant set of studies, however the evidence supporting the major claims of the manuscript is incomplete, particularly in highlighting a direct role for GLUT1 in monocytes. This work integrates an interesting set of observations that will be of interest to the Plasmodium and pathogenesis communities with an expanded set of experiments.

eLife Assessment

This important study demonstrates that Mycobacterium tuberculosis suppresses protective Th17/IL-17 responses in C57BL/6 mice via a Tbet-dependent mechanism involving the virulence factors ESX-1 and PDIM, as mutants lacking these factors induce significantly higher IL-17-producing CD4 T cells and IL-17A in the lungs compared to wild-type bacteria. The experiments are rigorous and well-designed, combining host knockouts and bacterial mutants to yield solid evidence pointing to cross-regulation between Th1 and Th17 pathways, including reduced IL-23 in draining lymph node dendritic cells. However, some of the data on IFN-γ effects or lymph node-specific mechanisms are incomplete and require deeper mechanistic insight, such as direct T cell transcription factor analysis in lymph nodes and broader host validation, to strengthen the work. Overall, the findings provide insight into how bacterial virulence factors limit Th17 induction, thereby promoting persistence, and will interest immunologists and TB researchers focused on host-pathogen balance and vaccine strategies.

eLife Assessment

AIRE has been well known to contribute to immune self-tolerance in the thymus by expressing auto-antigens; in this manuscript, the authors describe unexpected findings about the interaction of AIRE with AID in B cells, and its function in the immune system, thereby contributing to a fundamental understanding of the broader functions of AIRE. The strength of this manuscript is that, by employing biochemical and genetic experiments, the authors convincingly show interaction between AIRE and AID and subsequent AIRE's function in the GC responses. However, two weak points exist: first, the connection between AIRE, auto-anti IL17 Abs, and IL17-positive effector T cells, and second, like the thymus, expression of auto-antigens by AIRE in the GC B cells has not been tested.