Immunology

Redirection of SARS-CoV-2 to phagocytes by intranasal sACE2-Fc as a universal decoy confers complete prophylactic protection

1. Jingyi Wang
2. Jiangchuan Li
3. Alex W Chin
4. Bin Luo
5. Junkang Wei
6. Jiale Qiu
7. Jianwei Ren
8. Yin Xia
9. Thomas Braun
10. Leo LM Poon
11. Bo Feng

• Curated by eLife

  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 biodistribution studies and macrophage depletion assays, and demonstration of antibody-dependent cellular phagocytosis as the primary clearance mechanism. However, there are some gaps that require attention, including the need for comparison with a previously reported ACE2 decamer, inclusion of control molecules, insufficient discussion of potential limitations such as off-target binding and immunogenicity risks, and lack of clarity regarding certain methodological aspects.

Reviewed by eLife

Bivalent mRNA booster encoding virus-like particles elicits potent polyclass RBD antibodies in pre-vaccinated mice

1. Chengcheng Fan
2. Alexander A Cohen
3. Kim-Marie A Dam
4. Annie V Rorick
5. Ange-Célia I Priso Fils
6. Zhi Yang
7. Priyanthi NP Gnanapragasam
8. Luisa N Segovia
9. Kathryn E Huey-Tubman
10. Woohyun J Moon
11. Paulo JC Lin
12. Pamela J Bjorkman
13. Magnus AG Hoffmann

• Curated by eLife

  eLife Assessment

  This report provides useful evidence that EABR mRNA is at least as effective as standard S mRNA vaccines for the SARS-CoV-2 booster vaccine. Although the methodology and the experimental approaches are solid, the inconsistent statistical significance throughout the study presents limitations in interpreting the results. Also, the absence of results showing possible mechanisms underlying the lack of benefit with EABR in the pre-immune makes the findings mostly observational.

Reviewed by eLife

Immunoglobulin M regulates airway hyperresponsiveness independent of T helper 2 allergic inflammation

1. Sabelo Hadebe
2. Anca Flavia Savulescu
3. Jermaine Khumalo
4. Katelyn Jones
5. Sandisiwe Mangali
6. Nontobeko Mthembu
7. Fungai Musaigwa
8. Welcome Maepa
9. Hlumani Ndlovu
10. Amkele Ngomti
11. Martyna Scibiorek
12. Javan Okendo
13. Frank Brombacher

• Curated by eLife

  eLife Assessment

  This important study demonstrates a reduction in airway hyperresponsiveness (one of the mechanisms of allergic asthma) in the absence of IgM in a house dust mite-induced mouse model of allergic asthma. While this result suggests a new mechanistic role for IgM, the proposed new function is not as yet robustly supported by the current experiments and thus the evidence remains incomplete. A connection between the findings and human disease is not established so far, but the study will be interest to clinical immunologists.

Reviewed by eLife

Male-Biased Cyp17a2 Governs Antiviral Sexual Dimorphism in Fish via STING Stabilization and Viral Protein Degradation

1. Long-Feng Lu
2. Bao-jie Cui
3. Sheng-Chi Shi
4. Yang-Yang Wang
5. Can Zhang
6. Xiao Xu
7. Meng-Ze Tian
8. Zhen-Qi Li
9. Na Xu
10. Zhuo-Cong Li
11. Dan-Dan Chen
12. Li Zhou
13. Gang Zhai
14. Zhan Yin
15. Shun Li

• Curated by eLife

  eLife Assessment

  This valuable study describes an interesting infection phenotype that differs between adult male and female zebrafish. The authors present data indicating that male-biased expression of Cyp17a2 mediates viral infection through STING and USP8 activity regulation. The authors present solid evidence linking this factor to direct and indirect antiviral outcomes through ubiquitination pathways. These findings raise interesting questions about immune mechanisms that underlie sex dimorphism and the selective pressures that might shape it.

Reviewed by eLife

The Impact of Malaria-Induced Neutrophil Subset Shift and a Link to Burkitt Lymphoma

1. Sharon Akinyi
2. Ronald K. Tonui
3. Titus K. Maina
4. Eddy Agwati
5. Cliff I. Oduor
6. Festus M. Njuguna
7. Kibet K. Keitany
8. Daniel Chepsiror
9. Cyrus Ayieko
10. Ann Moormann
11. Ann W. Kinyua
12. Catherine S. Forconi

Reviewed by PREreview

NK cells undergo transcriptional and functional reprogramming following Streptococcus pneumoniae infection

1. Júlia Torné
2. Claudia Chica
3. Tiphaine Camarasa
4. Bernd Jagla
5. Matilde Diaz Enes
6. Aymeric Zellner
7. Sébastien Mella
8. Valentina Libri
9. Mélanie Anne Hamon

Reviewed by PREreview

HIV-specific CD8+ T-cell proliferative response 24 weeks after early antiretroviral therapy initiation predicts the subsequent reduction of the viral reservoir

1. Pien M van Paassen
2. Alexander O Pasternak
3. Dita C Bolluyt
4. Karel A van Dort
5. Ad C van Nuenen
6. Irma Maurer
7. Brigitte Boeser-Nunnink
8. Ninée VEJ Buchholtz
9. Tokameh Mahmoudi
10. Cynthia Lungu
11. Reinout van Crevel
12. Casper Rokx
13. Jori Symons
14. Monique Nijhuis
15. Annelou van der Veen
16. Liffert Vogt
17. Michelle J Klouwens
18. Jan M Prins
19. Neeltje A Kootstra
20. Godelieve J de Bree

• Curated by eLife

  eLife Assessment

  The findings of this study are valuable as it demonstrates that when treatment is initiated during acute infection, HIV specific CD8 T cell responses are maintained long term and continued proliferative capacity of these cells may play a role in reducing HIV DNA levels. The evidence supporting the conclusions are solid with rigorous and advanced methodology used with the major limitations being that the findings are association level and do not meet strict criteria for causality. The work is of interest to the HIV cure field and suggests that enhancing early HIV specific CD8 T cell responses should be considered in the design of interventional cure strategies.

Reviewed by eLife

Direct contact between iPSC-derived macrophages and hepatocytes drives reciprocal acquisition of Kupffer cell identity and hepatocyte maturation

1. Christopher Zhe Wei Lee
2. Farah Tasnim
3. Xiaozhong Huang
4. Raman Sethi
5. Yoohyun Song
6. Tatsuya Kozaki
7. Sebastiaan De Schepper
8. Nicholas Ang
9. Ivy Low
10. You Yi Hwang
11. Jinmiao Chen
12. Hanry Yu
13. Florent Ginhoux

• Curated by eLife

  eLife Assessment

  This timely and fundamental study introduces a human iPSC-based co-culture system that models Kupffer cell-hepatocyte interactions and aims to recapitulate liver-specific immune-parenchymal dynamics. Direct contact between iMacs and iHeps promotes mutual tissue-specific maturation, with iHeps downregulating fetal genes while iMacs acquire a Kupffer cell-like profile. This convincing in vitro model holds significant promise and is a leap forward; future experimental understanding will enhance its translational impact.

Reviewed by eLife

Contrasting roles for IKK regulated inflammatory signalling pathways for development and maintenance of type 1 and adaptive γδ T cells

1. Farjana Islam
2. Cayman Williams
3. Thea Hogan
4. Louise Webb
5. Ines Boal-Carvalho
6. Benedict Seddon

• Curated by eLife

  eLife Assessment

  This study provides valuable insights into the role of the NF-kB and IKK signaling pathways in γδ T cell development and survival, using robust genetic mouse models. While the research is methodologically sound, some conclusions require further evidence, with incomplete analyses, particularly regarding cell-intrinsic effects and mechanistic details. Overall, the findings are significant for immunologists interested in innate-like T cell biology and advancing the understanding of γδ T cell differentiation and maintenance.

Reviewed by eLife

Ex vivo and in vivo CRISPR/Cas9 screenings identify the roles of protein N-glycosylation in regulating T-cell activation and functions

1. Yu Hong
2. Xiaofang Si
3. Wenjing Liu
4. Xueying Mai
5. Yu Zhang

• Curated by eLife

  eLife Assessment

  This valuable work investigates the role of protein N-glycosylation in regulating T-cell activation and function and suggests that B4GALT1 is a potential target for tumor immunotherapy. The strength of evidence is solid, and further mechanistic validation could be provided.

Reviewed by eLife