Immunology

HIV skews the SARS-CoV-2 B cell response towards an extrafollicular maturation pathway

1. Robert Krause
2. Jumari Snyman
3. Hwa Shi-Hsia
4. Daniel Muema
5. Farina Karim
6. Yashica Ganga
7. Abigail Ngoepe
8. Yenzekile Zungu
9. Inbal Gazy
10. Mallory Bernstein
11. Khadija Khan
12. Matilda Mazibuko
13. Ntombifuthi Mthabela
14. Dirhona Ramjit
15. COMMIT-KZN Team
16. Oliver Limbo
17. Joseph Jardine
18. Devin Sok
19. Ian A Wilson
20. Willem Hanekom
21. Alex Sigal
22. Henrik Kløverpris
23. Thumbi Ndung'u
24. Alasdair Leslie

• Curated by eLife

  Evaluation Summary:

  The authors investigate how HIV-1 infection affects the immune response in the context of SARS-CoV-2 infection by characterising the circulating B cell response. They conclude that people with HIV-1 infection, who become infected by SARS-CoV-2, produce B cell responses via an extra-follicular pathway to a greater degree than people who do not have HIV-1 infection. These findings imply that in HIV-1 infected individuals, long-term B cell and antibody responses against SARS-CoV-2 might not be as robust and durable compared to those in people without HIV-1 infection. The manuscript will be of interest to infectious disease specialists, virologists, and immunologists.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Enriched dietary saturated fatty acids induce trained immunity via ceramide production that enhances severity of endotoxemia and clearance of infection

1. Amy L Seufert
2. James W Hickman
3. Ste K Traxler
4. Rachael M Peterson
5. Trent A Waugh
6. Sydney J Lashley
7. Natalia Shulzhenko
8. Ruth J Napier
9. Brooke A Napier

• Curated by eLife

  Evaluation Summary:

  In this manuscript entitled "Dietary palmitic acid induces innate immune memory via ceramide production that enhances severity of acute septic shock and clearance of infection" Seufert and colleagues have investigated how saturated fatty acids increase susceptibility of the host in a murine model of LPS-mediated septic shock. Pretreatment of macrophages with palmitic acid (PA) was found to reprogram macrophages towards hyper-inflammatory phenotype, which was dependent on ceremide. Importantly, depletion of macrophages intracellular ceremide with oleic acid reversed their hyper-inflammatory phenotype. Interestingly, while PA was harmful in the LPS-acute septic shock model, it was beneficial in clearance of C. albicans in Rag-deficient mice lacking both B and T cells. While this is an exciting study, the presented data don't fully support the central hypothesis and the link with trained immunity is currently weak.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Human thymopoiesis produces polyspecific CD8+ α/β T cells responding to multiple viral antigens

1. Valentin Quiniou
2. Pierre Barennes
3. Vanessa Mhanna
4. Paul Stys
5. Helene Vantomme
6. Zhicheng Zhou
7. Federica Martina
8. Nicolas Coatnoan
9. Michele Barbie
10. Hang-Phuong Pham
11. Béatrice Clémenceau
12. Henri Vie
13. Mikhail Shugay
14. Adrien Six
15. Barbara Brandao
16. Roberto Mallone
17. Encarnita Mariotti-Ferrandiz
18. David Klatzmann

• Curated by eLife

  eLife assessment

  This paper reports on important observations regarding human CD8 T cells that express shared T cell receptors amongst individuals and exhibit poly-specificity directed mainly to several unrelated viral antigens. Although the majority of the claims are convincingly supported by results from both in silico and experimental approaches, mechanistic molecular details underlying poly-specificity remain incomplete. The results from these studies will enhance the ongoing debate on T cell specificity and potentially, will impact fields related to immunology, for example, immunoparasitology, cell biology, and vaccine development.

Reviewed by eLife

PTPN22 R620W gene editing in T cells enhances low-avidity TCR responses

1. Warren Anderson
2. Fariba Barahmand-pour-Whitman
3. Peter S Linsley
4. Karen Cerosaletti
5. Jane H Buckner
6. David J Rawlings

• Curated by eLife

  Evaluation Summary:

  PTPN22 is a protein tyrosine phosphatase which negatively regulates antigen receptor signaling. It has been proposed that several genetic variants of PTPN22 might be loss of function (LOF) variants, leading to hyper-responsive T cell proliferative and effector responses. The authors investigate how the PTPN22 R620W variant, associated with multiple autoimmune diseases, might contribute to breech of peripheral T cell tolerance. This work greatly advances and clarifies ongoing confusion of whether PTPN22 SNP(620W) is a LOF mutant.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Neutrophil-mediated fibroblast-tumor cell il-6/stat-3 signaling underlies the association between neutrophil-to-lymphocyte ratio dynamics and chemotherapy response in localized pancreatic cancer: A hybrid clinical-preclinical study

1. Iago de Castro Silva
2. Anna Bianchi
3. Nilesh U Deshpande
4. Prateek Sharma
5. Siddharth Mehra
6. Vanessa Tonin Garrido
7. Shannon Jacqueline Saigh
8. Jonathan England
9. Peter Joel Hosein
10. Deukwoo Kwon
11. Nipun B Merchant
12. Jashodeep Datta

• Curated by eLife

  Evaluation Summary:

  Iago De Castro et al, constitute an exciting study conveying to readers that neutrophil-to-lymphocyte ratio dynamics predict pancreatic cancer pathologic response to neoadjuvant therapy. Specifically, the authors aim to determine the effect of gemcitabine/paclitaxel and anti-Ly6G treatment on stromal T cells and CAF populations. They conclude that neutrophil-to-lymphocyte ratios are associated with survival following this treatment and use animal models to show metastatic effects allied to it. The authors attempt to convey that microenvironmental neutrophils could play a causal role in pancreatic cancer chemoresistance. It was agreed that while the discoveries are very interesting, the public could benefit from the authors improving: the relevance to the human condition, providing a stronger link to fibroblastic cell functional transitions, broadening the discussion regarding previous/related published studies, and strengthening the anti-Ly6G specificity proof within the provided data.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Maternal obesity blunts antimicrobial responses in fetal monocytes

1. Suhas Sureshchandra
2. Brianna M Doratt
3. Norma Mendza
4. Oleg Varlamov
5. Monica Rincon
6. Nicole E Marshall
7. Ilhem Messaoudi

• Curated by eLife

  eLife assessment

  This is an important manuscript that will be of interest to a broad range of researchers studying immunology, obesity and metabolism, as well as the links between maternal health and pathophysiological responses in the offspring. The comprehensive studies using RNA-seq, scRNA-seq, ATAC-seq and scATAC-seq in human umbilical cord monocytes represent an important resource for understanding the transcriptomic and epigenetic shifts in the monocytes of newborns. The experiments involving stimulation of monocytes with pathogens offer convincing evidence for the dysfunction of monocytes in the newborn.

Reviewed by eLife

Meningeal lymphatic drainage promotes T cell responses against Toxoplasma gondii but is dispensable for parasite control in the brain

1. Michael A Kovacs
2. Maureen N Cowan
3. Isaac W Babcock
4. Lydia A Sibley
5. Katherine Still
6. Samantha J Batista
7. Sydney A Labuzan
8. Ish Sethi
9. Tajie H Harris

• Curated by eLife

  Evaluation Summary:

  This manuscript tackles the timely and interesting research question of whether meningeal lymphatic drainage is required for the control of brain infection with Toxoplasma gondii. It contains a sophisticated experimental approach using cutting-edge methods, it has an easy-to-follow narrative, and comes up with an interesting albeit negative finding which the authors even tried to explain by an additional set of experiments. Although there are some limitations and weaknesses of the paper in its present form it will certainly contribute to the growing body of literature on how the once "immune-privileged" CNS is protected against environmental challenges.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Memory persistence and differentiation into antibody-secreting cells accompanied by positive selection in longitudinal BCR repertoires

1. Artem Mikelov
2. Evgeniia I Alekseeva
3. Ekaterina A Komech
4. Dmitry B Staroverov
5. Maria A Turchaninova
6. Mikhail Shugay
7. Dmitriy M Chudakov
8. Georgii A Bazykin
9. Ivan V Zvyagin

• Curated by eLife

  Evaluation Summary:

  By performing homeostatic longitudinal IgH repertoire analysis of human memory B cells and plasma cells, authors draw two major unique conclusions; first, a high degree of clonal persistence in individual memory B cell subsets with inter individual convergence in memory B and plasma cells; second, reactivation of persisting memory B cells with new rounds of affinity maturation during proliferation and differentiation into plasma cells. These conclusions provide a significant insight into how human memory B and plasma cells are generated in a homeostatic condition.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

The structure-selective endonucleases GEN1 and MUS81 mediate complementary functions in safeguarding the genome of proliferating B lymphocytes

1. Keith Conrad Fernandez
2. Laura Feeney
3. Ryan M Smolkin
4. Wei-Feng Yen
5. Allysia J Matthews
6. William Alread
7. John HJ Petrini
8. Jayanta Chaudhuri

• Curated by eLife

  Evaluation Summary:

  This manuscript is of interest to individuals working on genome stability and B lymphocyte development. Using knockouts for the genes encoding the structure-selective endonucleases GEN1 and MUS81 in mice, the authors show that the absence of both proteins is incompatible with embryonic development, with selective loss in mature B-cells inhibiting germinal center formation. This is the first study of these enzymes in an organismic context and in primary cells, revealing insight into the in vivo consequences of loss of MUS81 and GEN1 functions not previously accessible through studies in cultured cells.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Role of Rab5 early endosomes in regulating Drosophila gut antibacterial response

1. Manish Joshi
2. Annelise Viallat-Lieutaud
3. Julien Royet

Reviewed by Review Commons