Immunology

eLife Assessment

This manuscript presents a valuable antiviral approach using an engineered ACE2-Fc fusion protein that demonstrates broad-spectrum neutralization capacity against SARS-CoV-2 variants and achieves significant prophylactic protection in animal models through a novel Fc-mediated phagocytosis mechanism. The study provides convincing evidence for protective efficacy through rigorous in vivo validation in mice, mechanistic characterization via transcriptomic analysis and biodistribution studies, and demonstration of antibody-dependent cellular phagocytosis as the primary clearance mechanism mediated by the decoy. The work will be of interest to researchers working in vaccine development and associated immune responses.

eLife Assessment

This is a valuable study that investigates the role of the long non-coding RNA Dreg1 for the development, differentiation, or maintenance of group 2 ILC (ILC2). The authors generate Dreg1-/- mice and show solid evidence for a reduction of group 2 innate lymphoid cells (ILC2). However, the strength of evidence supporting and analysing the impact of Dreg1 on Gata3 expression, a transcription factor required for ILC2 cell fate decisions, remains incomplete. This study will be of interest to immunologists.

eLife Assessment

This paper provides a valuable observation that imiquimod, a compound often used to induce a psoriasis-like skin inflammation in mice, has a TLR7-independent effect acting through the unfolded protein response and binding to Gelsolin. However, the mechanism connecting Gelsolin to skin inflammation presented in this paper is incomplete and requires further investigation. These findings are of interest to the field of skin immunology.

eLife Assessment

This study provides valuable insights into how HIV-1 Env modulates the nanoscale organization and dynamics of the CXCR4 co-receptor on T cells, using quantitative imaging and functional approaches, the authors present convincing evidence that gp120 engagement promotes CD4-dependent clustering and altered mobility of CXCR4, distinct from the effects of the natural ligand CXCL12. Some concerns were raised regarding the interpretation of the single-particle tracking analyses, and additional clarification or analysis may help strengthen the conclusions. The physiological relevance of the findings could be further enhanced by validation with infectious virus and by more clearly integrating the CXCR4R334X mutant observations into the central mechanistic narrative. The work will be of interest to researchers studying HIV entry and membrane receptor organization.

[Editors' note: this paper was reviewed by Review Commons.]

eLife Assessment

This study introduces a valuable toolkit for zebrafish transgenesis, significantly enhancing the flexibility and efficiency of transgene generation for immunological applications. The authors provide convincing evidence through well-designed experiments, demonstrating the toolkit's utility in generating diverse and functional transgenic lines.

eLife Assessment

Findings from this study are considered fundamental because they identify amino acid uptake, cholesterol synthesis, and protein prenylation as key metabolic regulators of B cell activation, proliferation, and survival, advancing understanding of T-independent immune responses. The study links metabolic reprogramming directly to B cell function, highlighting how cellular metabolism supports immune fitness. The evidence is compelling, combining unbiased proteomic profiling with genetic and pharmacological validation to demonstrate causal roles for these pathways.

eLife Assessment

This is an important study that addresses the role of fever as a conserved response to viral infection. It demonstrates that the heat-shock factor, HSF1, is activated by increased temperature during fever to enhance the anti-viral immune response. The data provides compelling evidence for the conclusions and the work will be of interest to virologists, immunologists, and cell biologists.

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 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.