Immunology

Clonal stochasticity in early NK cell response to mouse cytomegalovirus is generated by mature subsets of varying proliferative ability

1. Darren Wethington
2. Saeed Ahmad
3. Marc Potempa
4. Giuseppe Giuliani
5. Oscar A Aguilar
6. Maheshwor Poudel
7. Simon Grassmann
8. William Stewart
9. Nicholas M Adams
10. Joseph C Sun
11. Lewis L Lanier
12. Jayajit Das

• Curated by eLife

  eLife Assessment

  This study combines mathematical models and experimental data to analyse the emergence of heterogeneity within clonal NK cell responses during antigen-specific cell expansion. Although it comprises different experimental data and tests different theoretical hypotheses, the main claims remain incomplete and would benefit from the consideration of several previous findings about clonal immune responses and corresponding mathematical approaches. The study presents valuable findings with the potential to provide key insights about NK cell development if proposed claims could be confirmed by additional analyses.

Reviewed by eLife

Soluble immune mediators orchestrate protective in vitro granulomatous responses across Mycobacterium tuberculosis complex lineages

1. Ainhoa Arbués
2. Sarah Schmidiger
3. Miriam Reinhard
4. Sonia Borrell
5. Sebastien Gagneux
6. Damien Portevin

• Curated by eLife

  eLife Assessment

  This study describes the impact of mycobacterial genetic diversity on host-infection phenotypes by assessing the effect of different M. tuberculosis lineages on granulomatous inflammation using a 3D in vitro granuloma model. Despite being descriptive and showing mostly correlative relationships, the findings are useful and provide some solid support regarding the functional impact of M. tuberculosis's natural diversity on host-pathogen interactions. The study will interest researchers working on mycobacteria and motivate future studies to understand how genetic diversity influences virulence and immunity outcomes.

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

  Studying several allergens in different mouse strains, the authors assessed the role of IgM in airway inflammatory responses and show that IgM deficient mice have reduced airway hyperresponsiveness. Although the findings are useful and interesting and among others show the expression of a protein that regulates actin in smooth cells, the study remains incomplete as the data and analyses only partly support their primary claim.

Reviewed by eLife

Extracellular matrix phenotyping by imaging mass cytometry defines distinct cellular matrix environments associated with allergic airway inflammation

1. J E Parkinson
2. M Ghafoor
3. R J Dodd
4. H E Tompkins
5. M Fergie
6. M Rattray
7. J E Allen
8. T E Sutherland

Reviewed by Review Commons

Inhibiting NINJ1-dependent plasma membrane rupture protects against inflammasome-induced blood coagulation and inflammation

1. Jian Cui
2. Hua Li
3. Dien Ye
4. Guoying Zhang
5. Yan Zhang
6. Ling Yang
7. Martha MS Sim
8. Jeremy P Wood
9. Yinan Wei
10. Zhenyu Li
11. Congqing Wu

• Curated by eLife

  eLife Assessment

  The authors aim to elucidate the mechanism by which pyroptosis (through the formation of Gasdermin D (GSDMD) pores in the plasma membrane) contributes to increased release of procoagulant Tissue Factor-containing microvesicles. The data offers solid mechanistic insights as to the interplay between pyroptosis and microvesicle release with NINJ1. The study provides useful insights into the potential of targeting Ninj1 as a therapeutic strategy.

Reviewed by eLife

Newly discovered and conserved role of IgM against viral infection in an early vertebrate

1. Weiguang Kong
2. Xinyou Wang
3. Guangyi Ding
4. Peng Yang
5. Yong Shi
6. Chang Cai
7. Xinyi Yang
8. Gaofeng Cheng
9. Fumio Takizawa
10. Zhen Xu

• Curated by eLife

  eLife Assessment

  This important study explores the conserved role of IgM in both systemic and mucosal antiviral immunity in teleosts, challenging established views on the differential roles of IgT and IgM. The findings have theoretical and practical implications for immunology and aquaculture. However, the strength of the evidence is incomplete due to insufficient validation of the monoclonal antibodies used to deplete IgM, which limits confidence in the main claims. Addressing these methodological weaknesses would significantly enhance the study's impact.

Reviewed by eLife

Discovery of a Potent and Selective Inhibitor of Human NLRP3 with a Novel Binding Modality and Mechanism of Action

1. Kevin Wilhelmsen
2. Aditi Deshpande
3. Sarah Tronnes
4. Maitriyee Mahanta
5. Matthew Banicki
6. Mary Cochran
7. Samantha Cowdin
8. Kristen Fortney
9. George Hartman
10. Robert Hughes
11. Rusty Montgomery
12. Claudia Portillo
13. Paul Rubin
14. Yan Wang
15. Shijun Yan
16. Barry A Morgan
17. Assem Duisembekova
18. Romane Riou
19. Michael Marleaux
20. Inga V. Hochheiser
21. Hannes Buthmann
22. Dominic Ferber
23. Wei Wang
24. Melanie Cranston
25. Chloe M. McKee
26. Thea Mawhinney
27. Emma McKay
28. Bénédicte F. Py
29. Matthias Geyer
30. Rebecca C. Coll

Reviewed by preLights

SIV-specific neutralizing antibody induction following selection of a PI3K drive-attenuated nef variant

1. Hiroyuki Yamamoto
2. Tetsuro Matano

• Curated by eLife

  eLife Assessment

  Yamamoto and Matano provide convincing evidence that a G63E/R CD8+ T-cell escape mutation in the accessory viral protein Nef promote the induction of neutralizing antibody (nAb) responses in rhesus macaques infected with SIVmac239, which is usually largely resistant to neutralization. Functional analyses support that this mutation specifically impairs Nef`s ability to stimulate PI3K/Akt/mTORC2 signalling. This important study suggests that the accessory viral protein Nef impairs B cell function and effective humoral immune responses and is of interest for researchers and physicians interested in HIV/AIDS and vaccine development.

Reviewed by eLife

Genome Restructuring around Innate Immune Genes in Monocytes in Alcohol-associated Hepatitis

1. Adam Kim
2. Megan R McMullen
3. Annette Bellar
4. David Streem
5. Jaividhya Dasarathy
6. Nicole Welch
7. Srinivasan Dasarathy

• Curated by eLife

  eLife Assessment

  The manuscript addresses the 3D chromatin architecture in monocytes from patients with alcohol-associated hepatitis and its relationship to enhanced transcription of innate immune genes. While the concept and methodological approach are appealing, the evidence is incomplete as a result of insufficient sample sizes as well as other significant analytical concerns.

Reviewed by eLife

DGKα and ζ Deficiency Causes Regulatory T-Cell Dysregulation, Destabilization, and Conversion to Pathogenic T-Follicular Helper Cells to Trigger IgG1-Predominant Autoimmunity

1. Lei Li
2. Hongxiang Huang
3. Hongxia Wang
4. Yun Pan
5. Huishan Tao
6. Shimeng Zhang
7. Peer W.F. Karmaus
8. Michael B. Fessler
9. John W. Sleasman
10. Xiao-Ping Zhong

• Curated by eLife

  eLife Assessment

  This study presents a valuable finding on the signaling mechanisms underlying Treg cell homeostasis by identifying the simultaneous requirement of diacylglycerol (DAG) kinases (DGK) alpha and zeta for Foxp3+ Treg cell function and follicular responses, with implications for the pathogenesis of some autoimmune diseases. Whereas data based on the characterization of double knock-out mice (for DGK alpha and zeta) is solid, showing the emergence of autoimmune manifestations, the study has gaps in its experimental approaches since it is not clear what can be attributed to the simultaneous DKGα and ζ deficiency, versus the individual deficiency of either one. Experiments on the pathogenic potential of the DKO Tregs in the absence of other T-cells were not presented and results on the role of CD25 downregulation and CD28-independent activation of Treg cells were not properly discussed. Nonetheless, the reported data would be of interest to immunologists working on T-cell intracellular signaling and autoimmunity.

Reviewed by eLife