Immunology

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

Unraveling the power of NAP-CNB’s machine learning-enhanced tumor neoantigen prediction

1. Almudena Mendez-Perez
2. Andres M Acosta-Moreno
3. Carlos Wert-Carvajal
4. Pilar Ballesteros-Cuartero
5. Ruben Sánchez-García
6. Jose R Macias
7. Rebeca Sanz-Pamplona
8. Ramon Alemany
9. Carlos Oscar Sorzano
10. Arrate Munoz-Barrutia
11. Esteban Veiga

• Curated by eLife

  eLife Assessment

  Veiga et al demonstrate the importance of incorporating RNAseq and machine learning approaches for neoantigen prediction. The evidence is convincing, and these findings contribute important information towards the selection of neoantigens for personalized antitumor vaccination.

Reviewed by eLife

Expression of a single inhibitory member of the Ly49 receptor family is sufficient to license NK cells for effector functions

1. Sytse J Piersma
2. Shasha Li
3. Pamela Wong
4. Michael D Bern
5. Jennifer Poursine-Laurent
6. Liping Yang
7. Diana L Beckman
8. Bijal A Parikh
9. Wayne M Yokoyama

• Curated by eLife

  eLife Assessment

  This study on mouse Ly49 receptors expressed on natural killer (NK) cells shows that Ly49A, in the presence of the corresponding MHC Class I allele, can lead to NK cell licensing, thereby providing valuable insights into the mechanisms of NK cell modulation by Ly49 receptors. The work may have significant implications for studies of human Killer-cell immunoglobulin-like receptors (KIR) expressing and other NK cells. Overall, the study was well-developed with convincing evidence.

Reviewed by eLife

Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis

1. Alexander J Knights
2. Easton C Farrell
3. Olivia M Ellis
4. Michelle J Song
5. C Thomas Appleton
6. Tristan Maerz

• Curated by eLife

  eLife assessment

  This study provides useful information by identifying the cell type (macrophages) in synovial tissues involved in the pathogenesis of post-traumatic osteoarthritis (OA) and clarifying distinct transcriptomic signatures that may be a good therapeutic target for OA. However, the analysis performed so far is incomplete, with a main weakness being the lack of data to confirm the authors' speculation about the underlying mechanisms.

Reviewed by eLife

Acquisition of an immunosuppressive microenvironment after CAR-T therapy drives T-cell dysfunction and resistance

1. Marianna Ponzo
2. Lorenzo Drufuca
3. Chiara Buracchi
4. Marco M. Sindoni
5. Silvia Nucera
6. Cristina Bugarin
7. Ramona Bason
8. Grazisa Rossetti
9. Raoul Bonnal
10. Cristian Meli
11. Benedetta Rambaldi
12. Federico Lussana
13. Silvia Ferrari
14. Alex Moretti
15. Giulia Risca
16. Christian Pellegrino
17. Markus G. Manz
18. Stefania Galimberti
19. Alessandro Rambaldi
20. Giuseppe Gaipa
21. Andrea Biondi
22. Massimiliano Pagani
23. Chiara F. Magnani

Reviewed by PREreview

T3SS translocon induces pyroptosis by direct interaction with NLRC4/NAIP inflammasome

1. Yan Zhao
2. Hanshuo Zhu
3. Jinqian Li
4. Hang Xu
5. Li Sun

• Curated by eLife

  eLife Assessment

  This important study shows that Type 3 secretion translocons in Edwardsiella tarda and other bacteria activate the NAIP-NLRC4 inflammasome. The data from cellular and biochemical experiments showing that EseB is required for activation of the NLRC4 inflammasome are convincing. This paper is broadly relevant to those investigating host-pathogen interactions in diverse organisms.

Reviewed by eLife

A VgrG2b fragment cleaved by caspase-11/4 promotes Pseudomonas aeruginosa infection through suppressing the NLRP3 inflammasome

1. Yan Qian
2. Qiannv Liu
3. Xiangyun Cheng
4. Chunlei Wang
5. Chun Kong
6. Mengqian Li
7. Chao Ren
8. Dong Jiang
9. Shuo Wang
10. Pengyan Xia

• Curated by eLife

  eLife Assessment

  This valuable study on Pseudomonas subverting host immunity identifies a new immune evasion strategy. There is solid evidence for the cleavage of VgrG2B by Caspase 11 and the generation of fragments that inhibit activity of the NLRP3 inflammasome. This work should be of interest to immunologists and microbiologists.

Reviewed by eLife

Fish CDK2 recruits Dtx4 to degrade TBK1 through ubiquitination in the antiviral response

1. Long-Feng Lu
2. Can Zhang
3. Zhuo-Cong Li
4. Bao-Jie Cui
5. Yang-Yang Wang
6. Ke-Jia Han
7. Xiao Xu
8. Chu-Jing Zhou
9. Xiao-Yu Zhou
10. Yue Wu
11. Na Xu
12. Xiao-Li Yang
13. Dan-Dan Chen
14. Xi-Yin Li
15. Li Zhou
16. Shun Li

• Curated by eLife

  eLife Assessment

  This valuable study uses zebrafish as a model to reveal a role for the cell cycle protein kinase CDK2 as a negative regulator of type I interferon signaling. The evidence supporting the authors' claims is convincing, including both in vivo and in vitro investigative approaches that corroborate a role for CDK2 in regulating TBK1 degradation. In this latest version, the authors included data addressing concerns raised by the reviewers at the first peer review round that strengthens the conclusions. This work will interest cell biologists, immunologists, and virologists.

Reviewed by eLife