Immunology

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

Uncovering the Heterogeneity and Ontogeny of Mouse Thymic Macrophages Reveals an Unexpected Early Checkpoint Role

1. Helen Wang
2. Vinothkumar Rajan
3. Anthony Wong
4. Slava Epelman
5. Juan Carlos Zúñiga-Pflücker

• Curated by eLife

  eLife Assessment

  This study characterizes the heterogeneity and developmental origins of macrophages in the thymus and offers tantalizing evidence of their potential involvement in the first step of T cell selection. The macrophage characterisation is interesting, although the evidence for the specific involvement of macrophages in beta-selection is incomplete, as alternative explanations have not been ruled out. These results provide an important advance that further our understanding of thymus biology, especially in view of the contribution of heterogenous thymic macrophage subpopulations.

Reviewed by eLife

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 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 C Matteucci
2. Nathalia PS Leite
3. Patricia A Assis
4. Isabella C Hirako
5. Francielle Pioto
6. Ogooluwa Ojelabi
7. Juliana E Toller-Kawahisa
8. Leonardo G Vaz
9. Diego I 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

Deubiquitinase USP-14 controls intestinal distension-induced immune activation in Caenorhabditis elegans via Wnt/β-catenin signaling

1. Annesha Ghosh
2. Jogender Singh

Reviewed by Review Commons

TGF-β drives the conversion of conventional NK cells into uterine tissue-resident NK cells to support murine pregnancy

1. Josselyn D Barahona
2. Liping Yang
3. D Michael Nelson
4. Wayne M Yokoyama

• Curated by eLife

  eLife Assessment

  The importance of uterine natural killer (NK) cells in reproductive success has been demonstrated in mice and humans; however, it is still unclear how uterine NK cells are developed. In this important manuscript, the authors provide convincing evidence that TGF-b signaling in NK cells supports normal pregnancy in mice by the conversion of conventional NK cells into uterine tissue-resident NK cells. Previous concerns have been addressed in this revised version.

Reviewed by eLife

Depletion of extracellular asparagine impairs self-reactive T cells and ameliorates autoimmunity in a murine model of multiple sclerosis

1. Peter Georgiev
2. Sheila Johnson
3. Kiran Kurmi
4. Song-Hua Hu
5. SeongJun Han
6. Dillon Patterson
7. Thao H Nguyen
8. Linglin Huang
9. Dan Liang
10. Naomi Goldman
11. Thomas Conway
12. Hannah Creasey
13. Jared Rowe
14. Marcia C Haigis
15. Arlene H Sharpe

• Curated by eLife

  eLife Assessment

  Non-essential amino acids such as glutamine have been known to be required for T cell general activation through sustaining basic biosynthetic processes, including nucleotide biosynthesis, ATP generation, and protein synthesis. In this important study, the authors found that extracellular asparagine (Asn) is required not only for T cells to generally refuel metabolic reprogramming, but to produce helper T cell lineage-specific cytokine, for instance, IL17. In particular, the importance of Asn in IL17 production was convincingly demonstrated in the mouse experimental autoimmune encephalomyelitei (EAE) model, mimicking human multiple sclerosis disease.

Reviewed by eLife