Immunology

HEB collaborates with TCR signaling to upregulate Id3 and enable γδT17 cell maturation in the fetal thymus

1. Johanna S Selvaratnam
2. Juliana Dutra Barbosa da Rocha
3. Vinothkumar Rajan
4. Helen Wang
5. Emily C Reddy
6. Miki S Gams
7. Jenny Jiahuan Liu
8. Cornelis Murre
9. David L Wiest
10. Cynthia J Guidos
11. Juan Carlos Zúñiga-Pflücker
12. Michele K Anderson

• Curated by eLife

  eLife Assessment

  The study provides important mechanistic insight into the transcriptional control of γδT17 development, elegantly demonstrating how HEB and Id3 act sequentially and cooperatively to regulate γδT17 cell specification and maturation. The study provides compelling evidence that advances the understanding of E-Id protein dynamics in thymic T cell specification. The work is comprehensive, technically rigorous, and conceptually clear, and will be of interest to immunologists, developmental biologists, and those studying the molecular underpinnings of physiological outcomes.

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 L 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, however the evidence supporting the major claims of the manuscript is incomplete, particularly in highlighting a direct role for GLUT1 in monocytes. This 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

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 demonstrates that Mycobacterium tuberculosis suppresses protective Th17/IL-17 responses in C57BL/6 mice via a Tbet-dependent mechanism involving the virulence factors ESX-1 and PDIM, as mutants lacking these factors induce significantly higher IL-17-producing CD4 T cells and IL-17A in the lungs compared to wild-type bacteria. The experiments are rigorous and well-designed, combining host knockouts and bacterial mutants to yield solid evidence pointing to cross-regulation between Th1 and Th17 pathways, including reduced IL-23 in draining lymph node dendritic cells. However, some of the data on IFN-γ effects or lymph node-specific mechanisms are incomplete and require deeper mechanistic insight, such as direct T cell transcription factor analysis in lymph nodes and broader host validation, to strengthen the work. Overall, the findings provide insight into how bacterial virulence factors limit Th17 induction, thereby promoting persistence, and will interest immunologists and TB researchers focused on host-pathogen balance and vaccine strategies.

Reviewed by eLife

A Germinal Center Checkpoint of AIRE in B Cells Limits Antibody Diversification

1. Jordan Z. Zhou
2. Bihui Huang
3. Bo Pei
4. Guang Wen Sun
5. Michael D. Pawlitz
6. Wei Zhang
7. Xinyang Li
8. Kati C. Hokynar
9. Fayi Yao
10. Madusha L. W. Perera
11. Shanqiao Wei
12. Simin Zheng
13. Lisa A. Polin
14. Janet M. Poulik
15. Annamari Ranki
16. Kai Krohn
17. Charlotte Cunningham-Rundles
18. Naibo Yang
19. Ashok S. Bhagwat
20. Kefei Yu
21. Pärt Peterson
22. Kai Kisand
23. Bao Q. Vuong
24. Andrea Cerutti
25. Kang Chen

• Curated by eLife

  eLife Assessment

  AIRE has been well known to contribute to immune self-tolerance in the thymus by expressing auto-antigens; in this manuscript, the authors describe unexpected findings about the interaction of AIRE with AID in B cells, and its function in the immune system, thereby contributing to a fundamental understanding of the broader functions of AIRE. The strength of this manuscript is that, by employing biochemical and genetic experiments, the authors convincingly show interaction between AIRE and AID and subsequent AIRE's function in the GC responses. However, two weak points exist: first, the connection between AIRE, auto-anti IL17 Abs, and IL17-positive effector T cells, and second, like the thymus, expression of auto-antigens by AIRE in the GC B cells has not been tested.

Reviewed by eLife

Contrasting roles for IKK regulated inflammatory signalling pathways for development and maintenance of type 1 and adaptive 𝛄δ T cells

1. Farjana Islam
2. Cayman Williams
3. Thea Hogan
4. Louise Webb
5. Ines Boal-Carvalho
6. Benedict Seddon

• Curated by eLife

  eLife Assessment

  This study reports important findings regarding the role of the NF-kB signaling pathway in the development and long-term survival of gamma delta T cells. The authors report disparate roles of IKK-dependent NF-kB activation in the development and long-term survival of gamma delta T cell subsets. The approach and methodology employed is convincing. This work will be of great interest to immunologists interested in innate-like T cell biology and in T cell development.

Reviewed by eLife

Synaptotagmin 1 and Synaptotagmin 7 promote MR1-mediated presentation of Mycobacterium tuberculosis antigens

1. Se-Jin Kim
2. Jessie C Peterson
3. Andrew J Olive
4. Fikadu G Tafesse
5. Corinna A Kulicke
6. Elham Karamooz
7. David M Lewinsohn

• Curated by eLife

  eLife Assessment

  This useful study examines the contribution of synaptotagmin 1 and synaptotagmin 7 to metabolite antigen presentation to mucosal-associated invariant T (MAIT) cells; it begins to address a critical gap in our understanding of the antigen presentation mechanisms of these cells. Strengths of the study include the use of Mtb to study the dynamics of antigen presentation to MAIT cells instead of a synthetic antigen. The strength of the evidence to support the conclusion is solid.

Reviewed by eLife

Ex vivo and in vivo CRISPR/Cas9 screenings identify the roles of protein N-glycosylation in regulating T-cell activation and functions

1. Yu Hong
2. Xiaofang Si
3. Wenjing Liu
4. Xueying Mai
5. Yu Zhang

• Curated by eLife

  eLife Assessment

  The important study uses genome-wide CRISPR/Cas9 screenings to identify a novel target B4GALTZ1 that is implicated in modulating CD8+ T cell function in the context of anti-tumor immunity. The strength of evidence is solid but could benefit from more detail, particularly to verify the efficiency of knockout in their single gene KO lines and identification of N-glycosylation sites of TCR and CD8s. This work highlights the role of protein N-glycosylation, particularly B4GALT1 deficiency, in regulating CD8 function and anti-tumor immunity.

Reviewed by eLife

Daytime variation in SARS-CoV-2 infection and cytokine production

1. Aïssatou Bailo Diallo
2. Laetitia Gay
3. Benjamin Coiffard
4. Marc Leone
5. Soraya Mezouar
6. Jean-Louis Mege

Reviewed by Rapid Reviews Infectious Diseases, ScreenIT

Pre-existing YFV-17D immunity mediates T cell cross-protection against DENV-2 infection

1. Prince Baffour Tonto
2. Sebastian Gallon
3. Reem Alatrash
4. Wei-Kung Wang
5. Bobby Brooke Herrera

Reviewed by Rapid Reviews Infectious Diseases, PREreview

High titers and low fucosylation of early human anti–SARS-CoV-2 IgG promote inflammation by alveolar macrophages

1. Willianne Hoepel
2. Hung-Jen Chen
3. Chiara E. Geyer
4. Sona Allahverdiyeva
5. Xue D. Manz
6. Steven W. de Taeye
7. Jurjan Aman
8. Lynn Mes
9. Maurice Steenhuis
10. Guillermo R. Griffith
11. Peter I. Bonta
12. Philip J.M. Brouwer
13. Tom G. Caniels
14. Karlijn van der Straten
15. Korneliusz Golebski
16. René E. Jonkers
17. Mads D. Larsen
18. Federica Linty
19. Jan Nouta
20. Cindy P.A.A. van Roomen
21. Frank E.H.P. van Baarle
22. Cornelis M. van Drunen
23. Gertjan Wolbink
24. Alexander P.J. Vlaar
25. Godelieve J. de Bree
26. Rogier W. Sanders
27. Lisa Willemsen
28. Annette E. Neele
29. Diederik van de Beek
30. Theo Rispens
31. Manfred Wuhrer
32. Harm Jan Bogaard
33. Marit J. van Gils
34. Gestur Vidarsson
35. Menno de Winther
36. Jeroen den Dunnen

Reviewed by Rapid Reviews Infectious Diseases, ScreenIT, preLights