Immunology

Caspase-1 activates gasdermin A in non-mammals

1. Zachary Paul Billman
2. Stephen Bela Kovacs
3. Bo Wei
4. Kidong Kang
5. Ousmane H Cissé
6. Edward A Miao

• Curated by eLife

  eLife assessment

  This study presents valuable insights into the evolution of the gasdermin family, making a strong case that a GSDMA-like gasdermin activated by caspase-1 cleavage was already present in early land vertebrates. Convincing biochemical evidence is provided that extant avian, reptilian, and amphibian GSDMA proteins can still be activated by caspase-1 and upon cleavage induce pyroptosis-like cell death -- at least that they do so in the context of human cell lines. The caspase-1 cleavage site has only been lost in mammals, which use the more recently evolved GSDMD as a caspase-1 cleavable pyroptosis inducer. The presented work will be of considerable interest to scientists working on the evolution of cell death pathways, or on cell death regulation in non-mammalian vertebrates.

Reviewed by eLife

Murine alveolar macrophages rapidly accumulate intranasally administered SARS-CoV-2 Spike protein leading to neutrophil recruitment and damage

1. Chung Park
2. Il-Young Hwang
3. Serena Li-Sue Yan
4. Sinmanus Vimonpatranon
5. Danlan Wei
6. Don Van Ryk
7. Alexandre Girard
8. Claudia Cicala
9. James Arthos
10. John H Kehrl

• Curated by eLife

  eLife assessment

  This paper investigates the impact of intranasal instillation of SARS CoV2 spike protein in mouse models of lung inflammation. The authors conclude that the spike protein can interact with macrophages through carbohydrate recognition and can induce recruitment and NETosis of neutrophils, contributing to lung inflammation. They also use the cremaster muscle model to investigate effect of the spike proteins on neutrophil dynamics and death using intravital microscopy. Given that mucosal vaccines using SARS CoV2 spike variants could be envisioned as desirable, the observation that spike can induce lung/mucosal inflammation even without an adjuvant is important. Despite limitations of some loose terminology and some weak controls, the key observations are solid and demand further attention given the importance of the antigen.

Reviewed by eLife

RBP-J regulates homeostasis and function of circulating Ly6Clo monocytes

1. Tiantian Kou
2. Lan Kang
3. Bin Zhang
4. Jiaqi Li
5. Baohong Zhao
6. Wenwen Zeng
7. Xiaoyu Hu

• Curated by eLife

  eLife assessment

  This study presents a valuable examination into the role Notch-RBP-J signalling in regulating monocyte subset homeostasis. The data were collected and analysed using solid and validated methodology and can be used as a starting point for exploring the mechanisms involved in RBP-J signalling in non-classical monocytes. The data presented strongly confirm the authors conclusions. However, this paper primarily focuses on providing a description, and additional studies are necessary to fully elucidate the mechanisms through which RBP-J deficiency contributes to the specific increase in Ly6Clo monocyte numbers in both the blood and lungs.

Reviewed by eLife

Neuronal NPR-15 modulates molecular and behavioral immune responses via the amphid sensory neuron-intestinal axis in C. elegans

1. Benson Otarigho
2. Anna Frances Butts
3. Alejandro Aballay

• Curated by eLife

  eLife assessment

  The important work by Aballay et al. significantly advances our understanding of how G protein-coupled receptors (GPCRs) regulate immunity and pathogen avoidance. The authors provide convincing evidence for the GPCR NPR-15 to mediate immunity by altering the activity of several key transcription factors. This work will be of broad interest to immunologists.

Reviewed by eLife

Stimulation-induced cytokine polyfunctionality as a dynamic concept

1. Kevin Portmann
2. Aline Linder
3. Klaus Eyer

• Curated by eLife

  eLife assessment

  This useful study uses a microfluidic method to evaluate the ability of single human white blood cells to produce combinations of cytokines and the evidence that this takes place is solid. The paper highlights polyfunctionality using data that are similar to a prior dataset from the same group. The authors comment that, in analysis of larger panels, single cells rarely make more than 2 or 3 cytokines so that investigation of 3 cytokines at a time is sufficient to investigate this phenomenon. Coupling this approach to other modes of single cell analysis may provide greater insight into what limits simultaneous production of multiple cytokines.

Reviewed by eLife

A specific innate immune response silences the virulence of Pseudomonas aeruginosa in a latent infection model in the Drosophila melanogaster host

1. Jing Chen
2. Guiying Lin
3. Kaiyu Ma
4. Zi Li
5. Samuel Liégeois
6. Dominique Ferrandon

Reviewed by Review Commons

Mast cell activation disrupts interactions between endothelial cells and pericytes during early life allergic asthma

1. Régis Joulia
2. Franz Puttur
3. Helen Stölting
4. William J. Traves
5. Lewis J. Entwistle
6. Anastasia Voitovich
7. Minerva Garcia Martín
8. May Al-Sahaf
9. Katie Bonner
10. Elizabeth Scotney
11. Philip L. Molyneaux
12. Richard J. Hewitt
13. Simone A. Walker
14. Laura Yates
15. Sejal Saglani
16. Clare M. Lloyd

Reviewed by Arcadia Science

Inhibition of the UFD-1-NPL-4 complex triggers an aberrant immune response in Caenorhabditis elegans

1. Rajneesh Rao
2. Alejandro Aballay
3. Jogender Singh

• Curated by eLife

  eLife assessment

  In this valuable study, the authors investigate the role of the UFD-1/NPL-4 complex in the response of C. elegans to infection. While the work is of interest to the field, several pieces of evidence are incomplete, including a lack of validation of the inferences from the RNAi experiments with mutant analyses. There is also the question whether the UFD-1/NPL-4 complex might be better described as regulating "tolerance" to infection instead of inflammation.

Reviewed by eLife

Nifuroxazide suppresses PD-L1 expression and enhances the efficacy of radiotherapy in hepatocellular carcinoma

1. Tiesuo Zhao
2. Pengkun Wei
3. Congli Zhang
4. Shijie Zhou
5. Lirui Liang
6. Shuoshuo Guo
7. Zhinan Yin
8. Sichang Cheng
9. Zerui Gan
10. Yuanling Xia
11. Yongxi Zhang
12. Sheng Guo
13. Jiateng Zhong
14. Zishan Yang
15. Fei Tu
16. Qianqing Wang
17. Jin Bai
18. Feng Ren
19. Zhiwei Feng
20. Huijie Jia

• Curated by eLife

  eLife assessment

  This valuable study evaluates the effects of nifuroxazide on radiotherapy for the treatment of hepatocellular carcinoma. Solid evidence is provided to support the conclusion that nifuroxazide facilitates the downregulation of PD-L1 and may improve therapy outcomes when combined with radiotherapy, though the inclusion of additional cell lines and animal models would have strengthened the study. This work will be of interest to cancer biologists and those working in immuno-oncology.

Reviewed by eLife

Paradoxical imbalance between activated lymphocyte protein synthesis capacity and rapid division rate

1. Mina O Seedhom
2. Devin Dersh
3. Jaroslav Holly
4. Mariana Pavon-Eternod
5. Jiajie Wei
6. Matthew Angel
7. Lucas Shores
8. Alexandre David
9. Jefferson Santos
10. Heather Hickman
11. Jonathan W Yewdell

• Curated by eLife

  eLife assessment

  This study addresses how protein synthesis in activated lymphocytes keeps up with their rapid division, with important findings that are of significance to cell biologists and immunologists endeavouring to understand the 'economy' of the immune system. The work is supported by solid data. Because it proposes non-conventional mechanisms, the study sets the scene for further work in this area.

Reviewed by eLife