Immunology

A neutrophil–B-cell axis impacts tissue damage control in a mouse model of intraabdominal bacterial infection via Cxcr4

1. Riem Gawish
2. Barbara Maier
3. Georg Obermayer
4. Martin L Watzenboeck
5. Anna-Dorothea Gorki
6. Federica Quattrone
7. Asma Farhat
8. Karin Lakovits
9. Anastasiya Hladik
10. Ana Korosec
11. Arman Alimohammadi
12. Ildiko Mesteri
13. Felicitas Oberndorfer
14. Fiona Oakley
15. John Brain
16. Louis Boon
17. Irene Lang
18. Christoph J Binder
19. Sylvia Knapp

• Curated by eLife

  Evaluation Summary:

  This experiment investigated the link between the role of B lymphocytes to neutrophils for the achievement of LPS tolerance. The authors found that B cells can modulate the tissue-damaging properties of neutrophil leukocytes by influencing neutrophil Cxcr4 signaling in a mouse model of bacterial sepsis.

  (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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Plasmodium-encoded murine IL-6 impairs liver stage infection and elicits long-lasting sterilizing immunity

1. Selma Belhimeur
2. Sylvie Briquet
3. Roger Peronet
4. Jennifer Pham
5. Pierre-Henri Commere
6. Pauline Formaglio
7. Rogerio Amino
8. Artur Scherf
9. Olivier Silvie
10. Salaheddine Mecheri

Reviewed by Review Commons

Transient cell-in-cell formation underlies tumor relapse and resistance to immunotherapy

1. Amit Gutwillig
2. Nadine Santana-Magal
3. Leen Farhat-Younis
4. Diana Rasoulouniriana
5. Asaf Madi
6. Chen Luxenburg
7. Jonathan Cohen
8. Krishnanand Padmanabhan
9. Noam Shomron
10. Guy Shapira
11. Annette Gleiberman
12. Roma Parikh
13. Carmit Levy
14. Meora Feinmesser
15. Dov Hershkovitz
16. Valentina Zemser-Werner
17. Oran Zlotnik
18. Sanne Kroon
19. Wolf-Dietrich Hardt
20. Reno Debets
21. Nathan Edward Reticker-Flynn
22. Peleg Rider
23. Yaron Carmi

• Curated by eLife

  Evaluation Summary:

  Although immunotherapy has revolutionized the cancer field, most tumors do not respond, and in those that do respond, acquired resistance is often inevitable. Several mechanisms have been proposed to be involved in acquired resistance to immunotherapy. In the present study, the authors show that tumor cells from multi-cellular structures protect the inner core of tumor cells via the prevention of penetration by lytic molecules. The formation of these structures is mediated by anti-tumor T cells even with tumors that have retained their immunogenic neoantigens. This work identifies a novel possible resistance mechanism to immune-mediated tumor killing.

  (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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infection

1. Ryan Zander
2. Achia Khatun
3. Moujtaba Y Kasmani
4. Yao Chen
5. Weiguo Cui

• Curated by eLife

  Evaluation Summary:

  This study by Zander et al provides a valuable transcriptomic resource of murine CD4 T cell subsets in chronic viral infection. This study will be of broad interest to a wide range of researchers focused on studying CD4 T cell biology.

  (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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

HLJ1 amplifies endotoxin-induced sepsis severity by promoting IL-12 heterodimerization in macrophages

1. Wei-Jia Luo
2. Sung-Liang Yu
3. Chia-Ching Chang
4. Min-Hui Chien
5. Ya-Ling Chang
6. Keng-Mao Liao
7. Pei-Chun Lin
8. Kuei-Pin Chung
9. Ya-Hui Chuang
10. Jeremy JW Chen
11. Pan-Chyr Yang
12. Kang-Yi Su

• Curated by eLife

  Evaluation Summary:

  Wei- Jai et al., demonstrate the protein Human liver DnaJ-like protein (HLJ1) converts misfolded IL-12p35 homodimers to monomers in sepsis. This contributes to increased IL-12 activity, in macrophages which in turn leads to an increased production of IFN-gamma production and lethality in mice. This study suggests that HLJ1 plays an role in regulating IFN dependent mortality and future studies may determine a therapeutic role in blocking this protein.

  (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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3

1. Rémi Porte
2. Rita Silva-Gomes
3. Charlotte Theroude
4. Raffaella Parente
5. Fatemeh Asgari
6. Marina Sironi
7. Fabio Pasqualini
8. Sonia Valentino
9. Rosanna Asselta
10. Camilla Recordati
11. Marta Noemi Monari
12. Andrea Doni
13. Antonio Inforzato
14. Carlos Rodriguez-Gallego
15. Ignacio Obando
16. Elena Colino
17. Barbara Bottazzi
18. Alberto Mantovani

• Curated by eLife

  Evaluation Summary:

  This submission represents a holistic approach to how pentraxin 3 (PTX3) modulates susceptibility to experimental infection by Streptococcus pneumoniae. The authors have built robust findings on the importance of PTX3 for the survival of mice and they have extensively investigated all different aspects of the mechanism of PTX3 protection. One main strength of the manuscript is its usage of bone marrow chimeras in addition to total as well as tissue-specific mouse strains that support their claims.

  (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

Tissue-specific modifier alleles determine Mertk loss-of-function traits

1. Yemsratch T Akalu
2. Maria E Mercau
3. Marleen Ansems
4. Lindsey D Hughes
5. James Nevin
6. Emily J Alberto
7. Xinran N Liu
8. Li-Zhen He
9. Diego Alvarado
10. Tibor Keler
11. Yong Kong
12. William M Philbrick
13. Marcus Bosenberg
14. Silvia C Finnemann
15. Antonio Iavarone
16. Anna Lasorella
17. Carla V Rothlin
18. Sourav Ghosh

• Curated by eLife

  Evaluation Summary:

  The authors show that a widely used knock-out mouse for Mertk carries multiple additional changes in its genome, affecting the expression of a number of genes besides Mertk. They show that, although the line was back-crossed to the C57 background, these changes are due to the original 129P2 genome of the embryonic stem cells in which the knock-out was originally created. Through the generation of two new knock-out mouse strains, in C57 embryonic stem cells, the authors here show only part of the phenotype of the original Mertk knock-out mouse can be reproduced. Overall, this study raises awareness as to the limitations of the Mertk-/- v1 model and limits direct inference of Mertk-/-v1 observed phenotypes to Mertk deficiency alone.

  (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

Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses

1. Sara G Dosil
2. Sheila Lopez-Cobo
3. Ana Rodriguez-Galan
4. Irene Fernandez-Delgado
5. Marta Ramirez-Huesca
6. Paula Milan-Rois
7. Milagros Castellanos
8. Alvaro Somoza
9. Manuel José Gómez
10. Hugh T Reyburn
11. Mar Vales-Gomez
12. Francisco Sánchez Madrid
13. Lola Fernandez-Messina

• Curated by eLife

  Evaluation Summary:

  This report identified NK-extracellular-vesicle (NK-EV)-associated microRNAs and characterized them by small RNA next-generation sequencing. They found that NK-EVs promote Th1 polarization and activation of monocyte and monocyte-derived dendritic cells. The findings are potentially important for understanding NK cell function.

  (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

SMAD4 and TGFβ are architects of inverse genetic programs during fate determination of antiviral CTLs

1. Karthik Chandiran
2. Jenny E Suarez-Ramirez
3. Yinghong Hu
4. Evan R Jellison
5. Zeynep Ugur
6. Jun Siong Low
7. Bryan McDonald
8. Susan M Kaech
9. Linda S Cauley

• Curated by eLife

  Evaluation Summary:

  The authors set out to investigate the roles of SMAD4 and TGFbeta in regulating memory CD8 T cell differentiation during viral infection. To achieve their goal, the authors utilized a variety of available tools including, gene expression, mice that lack certain regulatory genes, and different tissue tissue culture approaches. Although the in vitro experiments yielded interesting results that will interest students of T cell immunology/biology, there is an absence of results from in vivo studies that would validate the in vitro observations.

  (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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Neuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy

1. Chandra Sekhar Boddupalli
2. Shiny Nair
3. Glenn Belinsky
4. Joseph Gans
5. Erin Teeple
6. Tri-Hung Nguyen
7. Sameet Mehta
8. Lilu Guo
9. Martin L Kramer
10. Jiapeng Ruan
11. Honggge Wang
12. Matthew Davison
13. Dinesh Kumar
14. DJ Vidyadhara
15. Bailin Zhang
16. Katherine Klinger
17. Pramod K Mistry

• Curated by eLife

  Evaluation Summary:

  Patients with Gaucher disease can have significant and crippling neurological manifestations. The study uses novel mouse models of neurodegeneration associated with glucocerebrosidase 1 (GBA1) deficiency. It provides a detailed analysis of the alterations caused by targeted deletion of GBA1, including cellular, genetic and metabolic alterations in neurons, microglia, and infiltrating immune cells. The work defines novel mechanisms driving neuroinflammation in neuronopathic Gaucher disease.

  (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. The reviewers remained anonymous to the authors.)

Reviewed by eLife