Immunology

Vangl2 suppresses NF-κB signaling and ameliorates sepsis by targeting p65 for NDP52-mediated autophagic degradation

1. Jiansen Lu
2. Jiahuan Zhang
3. Huaji Jiang
4. Zhiqiang Hu
5. Yufen Zhang
6. Lian He
7. Jianwu Yang
8. Yingchao Xie
9. Dan Wu
10. Hongyu Li
11. Ke Zeng
12. Peng Tan
13. Qingyue Xiao
14. Zijing Song
15. Chenglong Pan
16. Xiaochun Bai
17. Xiao Yu

• Curated by eLife

  eLife assessment

  This valuable manuscript describes a novel role of Vangl2, a core planar cell polarity protein, in linking the NF-kB pathway to selective autophagic protein degradation in myeloid cells. The mechanistic studies provide convincing evidence that Vangl2 targets p65 for NDP52-mediated autophagic degradation, limiting inflammatory NF-kB response, with functional significance of the proposed mechanism in sepsis. Additional future studies dissecting autophagic Vangl2 functions in various myeloid subsets in the context of inflammation could be informative, and additional Vangl2 targets in the inflammatory pathway, including IKK2, could also be explored. Overall, this exciting study can advance our understanding of NF-kB control, particularly in the context of inflammatory diseases.

Reviewed by eLife

An arms race between 5’ppp-RNA virus and its alternative recognition receptor MDA5 in RIG-I-lost teleost fish

1. Shang Geng
2. Xing Lv
3. Weiwei Zheng
4. Tianjun Xu

• Curated by eLife

  eLife assessment

  This important study shows that in teleost fish, the RIG-I-like protein MDA5 can compensate for the absence of RIG-I by detecting 5'-triphosphorylated RNA. A fish virus containing such RNA can nevertheless evade MDA5 detection through a mechanism involving m6A methylation-induced silencing. The conclusions, which are supported by solid data, advance our understanding of antiviral immunity and virus-host conflicts in vertebrates.

Reviewed by eLife

Single-cell transcriptome and T cell receptor profiling of the tuberculin skin test

1. Carolin T. Turner
2. Joshua Rosenheim
3. Clare Thakker
4. Aneesh Chandran
5. Holly Wilson
6. Cristina Venturini
7. Gabriele Pollara
8. Benjamin M. Chain
9. Gillian S. Tomlinson
10. Mahdad Noursadeghi

Reviewed by PREreview

The bacterial quorum sensing signal 2’-aminoacetophenone rewires immune cell bioenergetics through the Ppargc1a/Esrra axis to mediate tolerance to infection

1. Arijit Chakraborty
2. Arunava Bandyopadhaya
3. Vijay K Singh
4. Filip Kovacic
5. Sujin Cha
6. William M Oldham
7. A Aria Tzika
8. Laurence G Rahme

• Curated by eLife

  eLife assessment

  This important study demonstrates that the Pseudomonas aeruginosa-derived quorum sensing signal, 2-aminoacetophenone, induces immune tolerization in macrophages by perturbing metabolism, particularly in the context of mitochondrial respiration and bioenergetics. The authors present convincing evidence for 2-aminoacetophenone-mediated reduction of pyruvate transport into mitochondria, with downstream effects that result in reduced ATP production in tolerized macrophages. The work will be of interest to those studying host-pathogen interactions.

Reviewed by eLife

Enkephalin-mediated modulation of basal somatic sensitivity by regulatory T cells in mice

1. Nicolas Aubert
2. Madeleine Purcarea
3. Julien Novarino
4. Julien Schopp
5. Alexis Audibert
6. Wangtianrui Li
7. Marie Fornier
8. Léonie Cagnet
9. Marie Naturel
10. Armanda Casrouge
11. Marie-Caroline Dieu-Nosjean
12. Nicolas Blanchard
13. Gilles Dietrich
14. Cedric Peirs
15. Gilles Marodon

• Curated by eLife

  eLife assessment

  This study presents a valuable finding on a new role of Foxp3+ regulatory T cells in sensory perception, which may have an impact on our understanding of somatosensory perception. The authors identified a previously unappreciated action of enkephalins released by immune cells in the resolution of pain and several upstream signals that can regulate the expression of the proenkephalin gene PENK in Foxp3+ Tregs. The generation of transgenic mice with conditional deletion of PENK in Foxp3+ cells and PENK fate-mapping is novel and generates compelling data; they also show a comprehensive analysis of Tregs in control and transgenic mice, longitudinal data on heat sensitivity and co-localization of PENK+ Tregs with thermal sensory neurons in the skin further supporting their hypothesis. The study would be of interest to the biologists working in the field of neuroimmunology and inflammation.

Reviewed by eLife

Circadian rhythms of macrophages are altered by the acidic tumor microenvironment

1. Amelia M Knudsen-Clark
2. Daniel Mwangi
3. Juliana Cazarin
4. Kristina Morris
5. Cameron Baker
6. Lauren M Hablitz
7. Matthew N McCall
8. Minsoo Kim
9. Brian J Altman

Reviewed by Review Commons

Defining mononuclear phagocyte distribution and behaviour in the zebrafish heart

1. Bethany Moyse
2. Joanna Moss
3. Laura Bevan
4. Aaron Scott
5. Valérie Wittamer
6. Rebecca J Richardson

• Curated by eLife

  eLife assessment

  The manuscript presented by Moyse and colleagues provides valuable insight into the origin, morphology, dynamics, and behavior of several populations of mononuclear phagocytes in the zebrafish heart. The study presents solid evidence through the use of transgenic lines and live imaging, although some limitations related to lineage tracing and molecular profiles should be considered. This work exemplifies the use of zebrafish as a model to study the role of leukocytes in cardiac development and regeneration and potentially draw broader interest to biologists working in immunology fields.

Reviewed by eLife

Longitudinal transcriptional changes reveal genes from the natural killer cell-mediated cytotoxicity pathway as critical players underlying COVID-19 progression

1. Matias A Medina
2. Francisco Fuentes-Villalobos
3. Claudio Quevedo
4. Felipe Aguilera
5. Raul Riquelme
6. Maria Luisa Rioseco
7. Sebastian Barria
8. Yazmin Pinos
9. Mario Calvo
10. Ian Burbulis
11. Camila Kossack
12. Raymond A Alvarez
13. Jose Luis Garrido
14. Maria Ines Barria

• Curated by eLife

  eLife assessment

  This valuable paper compares blood gene signature responses between small cohorts of individuals with mild and severe COVID-19. The authors provide solid evidence for distinct transcriptional profiles during early COVID-19 infections that may be predictive of severity, within the limitations of studying human patients displaying heterogeneity in infection timelines and limited cohort size.

Reviewed by eLife

Broadly inhibitory antibodies against severe malaria virulence proteins

1. Raphael A. Reyes
2. Sai Sundar Rajan Raghavan
3. Nicholas K. Hurlburt
4. Viola Introini
5. Ikhlaq Hussain Kana
6. Rasmus W. Jensen
7. Elizabeth Martinez-Scholze
8. Maria Gestal-Mato
9. Cristina Bancells Bau
10. Monica Lisa Fernández-Quintero
11. Johannes R. Loeffler
12. James Alexander Ferguson
13. Wen-Hsin Lee
14. Greg Michael Martin
15. Thor G. Theander
16. Isaac Ssewanyana
17. Margaret E. Feeney
18. Bryan Greenhouse
19. Sebastiaan Bol
20. Andrew B. Ward
21. Maria Bernabeu
22. Marie Pancera
23. Louise Turner
24. Evelien M. Bunnik
25. Thomas Lavstsen

Reviewed by Rapid Reviews Infectious Diseases

REL2 overexpression in the Anopheles gambiae midgut causes major transcriptional changes but fails to induce an immune response

1. Astrid Hoermann
2. Paolo Capriotti
3. Giuseppe Del Corsano
4. Maria Grazia Inghilterra
5. Tibebu Habtewold
6. Julia A. Cai
7. Gauri Sachiko Saini
8. Huong Nguyen
9. Nikolai Windbichler
10. George K. Christophides

Reviewed by PREreview