Immunology

β-glucan reprograms macrophages to attenuate efferocytosis of cancer cells

1. Alexandros Chatzis
2. Jakub Lukaszonek
3. Dimitris Lagos
4. Dave Boucher
5. Ioannis Kourtzelis

• Curated by eLife

  eLife Assessment

  This important study describes the effect of beta-glucan innate training of macrophages and its effect on uptake of tumour cells and on the production of inflammatory cytokines. The data are convincing and show decreased phagocytic activity of apoptotic tumour cells accompanied by lower levels of secreted IL-1β, and in vivo findings are also provided in the revision. This finding has potential impact on designing potential macrophage-targeted cancer immuno-therapeutic approaches.

Reviewed by eLife

Tuberculosis susceptibility in genetically diverse mice reveals functional diversity of neutrophils

1. Marietta M Ravesloot-Chavez
2. Erik Van Dis
3. Douglas Fox
4. Andrea Anaya-Sanchez
5. Scott Espich
6. Xammy Huu Nguyenla
7. Sagar Rawal
8. Helia Samani
9. Mallory Ballinger
10. Henry F Thomas
11. Dmitri I Kotov
12. Russell E Vance
13. Michael W Nachman
14. Sarah A Stanley

• Curated by eLife

  eLife Assessment

  This study provides valuable insights into the host's variable susceptibility to Mycobacterium tuberculosis, using a novel collection of wild-derived inbred mouse lines from diverse geographic locations, along with immunological and single-cell transcriptomic analyses. While the data are convincing, a deeper mechanistic investigation into neutrophil subset functions would have further enhanced the study. This work will interest microbiologists and immunologists in the tuberculosis field.

Reviewed by eLife

Lipid Peroxidation and Type I Interferon Coupling Fuels Pathogenic Macrophage Activation Causing Tuberculosis Susceptibility

1. Shivraj M Yabaji
2. Vadim Zhernovkov
3. Prasanna Babu Araveti
4. Suruchi Lata
5. Oleksii S Rukhlenko
6. Salam Al Abdullatif
7. Arthur Vanvalkenburg
8. Yuriy Alekseev
9. Qicheng Ma
10. Gargi Dayama
11. Nelson C Lau
12. W Evan Johnson
13. William R Bishai
14. Nicholas A Crossland
15. Joshua D Campbell
16. Boris N Kholodenko
17. Alexander A Gimelbrant
18. Lester Kobzik
19. Igor Kramnik

• Curated by eLife

  eLife Assessment

  Yabaji et al. reports a fundamental study highlighting the mechanistic connection for susceptibility to TB infection via the sst1 locus, this was shown to involve increased IFN and Myc production causing the down-regulation of anti-oxidant defence genes and chronic lipidation. Ultimately, lipid peroxidation may underlie infectivity and macrophage dysfunction. Overall, the data presented are compelling, supported by a well designed multi-omics approach and the findings will be of broad interest to researchers investigating the molecular mechanisms of TB infection.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife, Review Commons

Nociceptor Neurons Control Pollution-Mediated Neutrophilic Asthma

1. Jo-Chiao Wang
2. Amelia Kulle
3. Theo Crosson
4. Amin Reza Nikpoor
5. Surbhi Gupta
6. Anais Roger
7. Moutih Rafei
8. Ajitha Thanabalasuriar
9. Sebastien Talbot

• Curated by eLife

  eLife Assessment

  This important work shows that fine particulate matter exposure to the lungs led to nociceptor-dependent neutrophilic inflammation. Likely macrophage-neuronal crosstalk, via release of artemin from macrophages and activation of Gfra3 on the JNC neuron, potentiated the response. The data convincingly strengthens links between pollutants, immune and neural interactions.

Reviewed by eLife

Interleukin 10 controls the balance between tolerance, pathogen elimination and immunopathology in birds

1. Dominique Meunier
2. Ricardo Corona-Torres
3. Kay Boulton
4. Zhiguang Wu
5. Maeve Ballantyne
6. Laura Glendinning
7. Anum Ali Ahmad
8. Dominika Borowska
9. Lorna Taylor
10. Lonneke Vervelde
11. Jorge del Pozo
12. Marili Vasilogianni
13. José Jaramillo-Ortiz
14. Gonzalo Sanchez-Arsuaga
15. Androniki Psifidi
16. Fiona Tomley
17. Kellie A Watson
18. Michael J McGrew
19. Mark P Stevens
20. Damer P Blake
21. David A Hume

• Curated by eLife

  eLife Assessment

  IL-10 balances protective and deleterious immune functions in mice and humans, but if IL-10 also controls avian intestinal homeostasis remains unclear. Generating genetic knockouts, Meunier et al. established that a complete lack of IL-10 strengthened immunity against enteric bacteria in chickens, while also aggravating infection-inflicted inflammatory tissue damage and dysbiosis upon parasite infection, but unlike mouse models, IL-10 deficiency did not provoke spontaneous colitis in chickens. The findings presented are valuable, and the strength of evidence is convincing. The observation may have implications for the livestock industry and additional studies involving genetic knockouts may further unravel conserved and distinct avian IL-10 controls.

Reviewed by eLife

Beta-Glucan Modulates Monocyte Plasticity and Differentiation Capacity to Mitigate DSS-Induced Colitis

1. Yinyin Lv
2. Yanyun Fan
3. Qingxiang Gao
4. Qiongyun Chen
5. Yiqun Hu
6. Lin Wang
7. Huaxiu Shi
8. Ermei Chen
9. Qinyu Xu
10. Ying Cai
11. Qingqi Fan
12. Linying Li
13. Dan Du
14. Jianlin Ren
15. Shih-Chin Cheng
16. Hongzhi Xu

• Curated by eLife

  eLife Assessment

  This study presents valuable and compelling evidence that β-glucan-induced trained immunity can protect against intestinal inflammation by reprogramming innate immune cells toward a reparative phenotype. The authors employ a convincing combination of functional assays, adoptive transfers, and single-cell transcriptomics to uncover mechanistic insights and demonstrate the therapeutic potential of innate immune memory in IBD. While the work is robust, addressing the underlying epigenetic mechanisms and including additional controls would further reinforce the trained immunity-specific interpretation.

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 WF Karmaus
8. Michael B Fessler
9. John W Sleasman
10. Xiao-Ping Zhong

• Curated by eLife

  eLife Assessment

  This study presents an important 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

Xcr1+ type 1 conventional dendritic cells are essential mediators for atherosclerosis progression

1. Tianhan Li
2. Liaoxun Lu
3. Juanjuan Qiu
4. Xin Dong
5. Le Yang
6. Kexin He
7. Yanrong Gu
8. Binhui Zhou
9. Tingting Jia
10. Toby Lawrence
11. Marie Malissen
12. Guixue Wang
13. Rong Huang
14. Hui Wang
15. Bernard Malissen
16. Yinming Liang
17. Lichen Zhang

• Curated by eLife

  eLife Assessment

  This manuscript by Li, Lu et al., presents important findings on the role of cDC1 in atherosclerosis and their influence on the adaptive immune system. Using Xcr1Cre-Gfp Rosa26LSL-DTA ApoE-/- mouse models, these data convincingly reveal an unexpected, non-redundant role of the XCL1-XCR1 axis in mediating cDC1 contributions to atherosclerosis.

Reviewed by eLife

Synthetic auxotrophy reveals metabolic regulation of plasma cell generation, affinity maturation, and cytokine receptor signaling

1. Sung Hoon Cho
2. Shawna K Brookens
3. Ariel L Raybuck
4. Kaylor Meyer
5. Yeeun C Paik
6. Jennie Hamilton
7. Jingxin Li
8. Karel Kalecky
9. Chloe Park
10. Sakeenah L Hicks
11. John Karijolich
12. Teodoro H Bottiglieri
13. Jeffrey C Rathmell
14. Denis Mogilenko
15. Chris D Scharer
16. Mark R Boothby

• Curated by eLife

  eLife Assessment

  The authors addressed an important biological question, namely the role of glutamine metabolism in humoral responses, and they obtained solid conclusions. The strength of this study is that the authors used state-of-the-art transgenic mouse models together with in vitro analysis, thereby providing significant insights into the question posed. The following would strengthen the manuscript: i) adding more in-depth functionality/physiological relevance in the discussion part, and ii) regarding the experiments, the inclusion of more appropriate controls and a clearer and more accurate description of the methods.

Reviewed by eLife

Tumor-infiltrating CD27 ^- IgD ^- regulatory B cells suppress cytotoxic CD8 ⁺ T cell responses in renal cell carcinoma

1. Zara Baig
2. Isabella Withnell
3. Joseph C.F. Ng
4. Christopher J.M. Piper
5. Hannah F. Bradford
6. Antonio Rullan
7. Edward H. Arbe-Barnes
8. Camila G.X. de Brito
9. Alessandro Di Tullio
10. Thomas J. Mitchell
11. Hans J. Stauss
12. Maxine G.B. Tran
13. Franca Fraternali
14. Claudia Mauri

Reviewed by preLights