Immunology

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 Paik
6. Jennie Hamilton
7. Jingxin Li
8. Karel Kalecky
9. Chloe Park
10. Juyeon Lim
11. Sakeenah L Hicks
12. John Karijolich
13. Teodoro H Bottiglieri
14. Jeffrey C Rathmell
15. Denis Mogilenko
16. Christopher D Scharer
17. Mark R Boothby

• Curated by eLife

  eLife Assessment

  The authors addressed a significant 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 important insights into the question posed. The manuscript has been further substantiated by adding more appropriate experimental controls and describing more in-depth functionality/physiological relevance.

Reviewed by eLife

Tolerance to Lung Infection in TWIK2 K ⁺ Efflux Mediated Macrophage Trained Immunity

1. Josh Thompson
2. Yufan Li
3. Yuanling Song
4. Mohammad Anas
5. Jaewon Cho
6. Ki-Wook Kim
7. Asrar B. Malik
8. Jingsong Xu

• Curated by eLife

  eLife Assessment

  This study presents valuable data suggesting that ATP-induced modulation of alveolar macrophage (AM) functions is associated with NLRP3 inflammasome activation and enhanced phagocytic capacity. While the in vivo and in vitro data reveal an interesting phenotype, the evidence provided is incomplete and does not fully support the paper's conclusions. Additional investigations would be of value in complementing the data and strengthening the interpretation of the results. This study should be of interest to immunologists and the mucosal immunity community.

Reviewed by eLife

Fatty Acid Synthase associates with nuclear-derived cytoplasmic dsRNA molecules and influences antiviral innate immune response

1. Charline Pasquier
2. Mélanie Messmer
3. Lise Moroge
4. Lisanne Knol
5. Johana Chicher
6. Richard Patryk Ngondo
7. Sébastien Pfeffer
8. Erika Girardi

Reviewed by Review Commons

The C3–C3aR axis modulates trained immunity in alveolar macrophages

1. Alexander P Earhart
2. Alberto E Lopez
3. Josue I Hernandez
4. Aasritha Nallapu
5. Deebly Chavez
6. Sayahi Suthakaran
7. Brian Yang
8. Jungheun Hyun
9. Rafael Aponte Alburquerque
10. Marick Starick
11. Lorena Garnica
12. Ayse Naz Ozanturk
13. Rahul Kumar Maurya
14. Xiaobo Wu
15. Jeffrey Haspel
16. Jae Woo Lee
17. Jaime Hook
18. Hrishikesh S Kulkarni

• Curated by eLife

  eLife Assessment

  This study explores how complement protein C3 and its signalling may modulate immune training in alveolar macrophages. The findings are an important contribution to the field of trained immunity. The findings are convincingly supported by in vivo and ex vivo experiments, encompassing both pharmacological and genetic-based approaches.

Reviewed by eLife

Mycobacterium tuberculosis suppresses protective Th17 responses during infection

1. Alex Zilinskas
2. Amir Balakhmet
3. Douglas Fox
4. Heyuan Michael Ni
5. Carolina Agudelo
6. Helia Samani
7. Sarah A Stanley

• Curated by eLife

  eLife Assessment

  This important study investigates the mechanisms by which Mycobacterium tuberculosis suppresses protective Th17 differentiation during infection. Using ESX-1- and PDIM-deficient mutants of M. tuberculosis, which lack functional eccC1 and fadD28 respectively, the authors demonstrate that these virulence factors actively restrict IL-17 responses via a T-bet-dependent pathway, independent of overall bacterial attenuation or infection duration. While the precise molecular interactions by which ESX-1 and PDIM modulate Th17 differentiation warrant further elucidation, the experiments are rigorously designed, the findings are clearly presented, and the evidence is solid for a specific role for these factors in limiting protective IL-17 immunity in M. tuberculosis infection.

Reviewed by eLife

BATF controls IFN I production via DC-SCRIPT in plasmacytoid dendritic cells

1. Shafaqat Ali
2. Ritu Mann-Nüttel
3. Marcel Marson
4. Ben Leiser
5. Jasmina Hoffe
6. Regine J. Dress
7. Mahamudul Hasan Bhuyan
8. Patrick Petzsch
9. Karl Köhrer
10. Haifeng C. Xu
11. Philipp A. Lang
12. Shengbo Zhang
13. Michaël Chopin
14. Stephen L. Nutt
15. Judith Alferink
16. Stefanie Scheu

Reviewed by PREreview

Integrin-deficient T cell leukemia accumulates in the central nervous system

1. Samantha Y Lux
2. Cynthia Chen
3. Bibi S Subhan
4. Hyunsoo Chung
5. Martyna Okuniewska
6. Asha Y Caslin
7. Kathleen A Martin
8. Jennifer K Schiavo
9. Jonah B Vernejoul
10. Robert C Froemke
11. Michael Cammer
12. Susan R Schwab

• Curated by eLife

  eLife Assessment

  This study presents an important finding that loss or blockade of key integrins unexpectedly enhances central nervous system accumulation of T-cell acute lymphoblastic leukemia cells and may increase their sensitivity to chemotherapy. The evidence is convincing, supported by well-designed in vivo models, CRISPR-based perturbations, competitive assays, imaging, and complementary therapeutic experiments. However, the mechanistic basis linking integrin loss, altered spatial distribution, and increased proliferation remains incompletely defined, and the translational implications would be strengthened by additional survival studies and validation in more clinically relevant models.

Reviewed by eLife

The serine protease homolog Skanda modulates Toll-Phenoloxidase-mediated immunity in Drosophila

1. Sanjana Vasanth
2. Yang Wang
3. Nathan Klotz
4. Anzer Khan
5. Chao Xiong
6. Jean-Philippe Boquete
7. Tisheng Shan
8. Prince Kumar Sah
9. Haobo Jiang
10. Bruno Lemaitre

Reviewed by Review Commons

+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 C 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. It comprises different experimental data and extensively explores various mathematical models, to study NK cell turnover during acute immune responses and homeostatic turnover within murine cytomegalovirus infection (MCMV). This solid study presents valuable findings and provides relevant insights on heterogeneous NK cell development.

Reviewed by eLife

Reprogramming of host energy metabolism mediated by the TNF-iNOS-HIF-1α axis plays a key role in host resistance to Plasmodium infection

1. Kely Catarine Matteucci
2. Nathalia PS Leite
3. Patricia A Assis
4. Isabella Cristina Hirako
5. Franciele Pioto
6. Ogooluwa Ojelabi
7. Juliana E Toller-Kawahisa
8. Leonardo Gomes Vaz
9. Diego Luis Costa
10. João S da Silva
11. José C Alves-Filho
12. Ricardo T Gazzinelli

• Curated by eLife

  eLife Assessment

  This important study examines the role of TNF in modulating energy metabolism during parasite infection. The authors perform an elegant set of studies combining genetics, small molecule perturbation, and phenotypic experiments to highlight a role for glycolysis and glucose transport in control of parasitemia. This solid work integrates an interesting set of observations that will be of interest to the Plasmodium and pathogenesis communities with an expanded set of experiments.

Reviewed by eLife