Immunology

Mast cells promote pathology and susceptibility in tuberculosis

1. Ananya Gupta
2. Vibha Taneja
3. Javier Rangel Moreno
4. Nilofer Naqvi
5. Abhimanyu
6. Yun Tao
7. Mushtaq Ahmed
8. Kuldeep S Chauhan
9. Daniela Trejo-Ponce de León
10. Gustavo Ramírez-Martínez
11. Luis Jiménez-Alvarez
12. Cesar Luna-Rivero
13. Joaquin Zuniga
14. Deepak Kaushal
15. Shabaana A Khader

• Curated by eLife

  eLife Assessment

  In this useful study, the authors utilize published scRNA-seq data to highlight the potential importance of mast cells (MCs) in TB granulomas, presenting a solid comparative assessment of chymase- and tryptase-expressing MCs in the lungs of Mycobacterium tuberculosis-infected individuals and non-human primates. While the authors appropriately discussed the inconsistencies across models, adoptive transfer experiments in MC-deficient mice would substantially strengthen the causal link between MCs and TB outcomes, providing more direct functional validation of the proposed role of MCs in TB pathogenesis.

Reviewed by eLife, Arcadia Science

Ly6G+Granulocytes-derived IL-17 limits protective host responses and promotes tuberculosis pathogenesis

1. Priya Sharma
2. Raman Deep Sharma
3. Binayak Sarkar
4. Varnika Panwar
5. Mrinmoy Das
6. Lakshyaveer Singh
7. Neharika Jain
8. Shivam Chaturvedi
9. Lalita Mehra
10. Aditya Rathee
11. Shilpa Sharma
12. Shihui Foo
13. Andrea Lee
14. N Pavan Kumar
15. Prasenjit Das
16. Vijay Viswanathan
17. Hardy Kornfeld
18. Shanshan W Howland
19. Subash Babu
20. Vinay Nandicoori
21. Amit Singhal
22. Dhiraj Kumar

• Curated by eLife

  eLife Assessment

  This valuable study examines the role of IL17-producing Ly6G PMNs as a reservoir for Mycobacterium tuberculosis to evade host killing activated by BCG immunisation. The authors provide solid data reporting that IL17-producing polymorphonuclear neutrophils harbour a significant bacterial load in both wild-type and IFNg-/- mice and that targeting IL17 and Cox2 improved disease outcomes whilst enhancing BCG efficacy. The specific contribution of neutrophil-derived IL-17 to disease pathogenesis remains to be definitively established through direct demonstration of IL-17 production by neutrophils and targeted depletion studies.

Reviewed by eLife

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

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