bims-traimu 2024-06-16 papers

Issue of 2024–06–16
seven papers selected by
Yantong Wan, Southern Medical University

Cell Rep. 2024 Jun 06. pii: S2211-1247(24)00652-1. [Epub ahead of print]43(6): 114324

Tissue-resident trained immunity in hepatocytes protects against septic liver injury in zebrafish.

Zhuang Wang, Yuanyuan Liu, Jing Hu, Xinwei You, Jin Yang, Yuanxing Zhang, Qin Liu, Dahai Yang.

Trained immunity is classically characterized by long-term functional reprogramming of innate immune cells to combat infectious diseases. Infection-induced organ injury is a common clinical severity phenotype of sepsis. However, whether the induction of trained immunity plays a role in protecting septic organ injury remains largely unknown. Here, through establishing an in vivo β-glucan training and lipopolysaccharide (LPS) challenge model in zebrafish larvae, we observe that induction of trained immunity could inhibit pyroptosis of hepatocytes to alleviate septic liver injury, with an elevated trimethyl-histone H3 lysine 4 (H3K4me3) modification that targets mitophagy-related genes. Moreover, we identify a C-type lectin domain receptor in zebrafish, named DrDectin-1, which is revealed as the orchestrator in gating H3K4me3 rewiring-mediated mitophagy activation and alleviating pyroptosis-engaged septic liver injury in vivo. Taken together, our results uncover tissue-resident trained immunity in maintaining liver homeostasis at the whole-animal level and offer an in vivo model to efficiently integrate trained immunity for immunotherapies.

Keywords: CP: Immunology; H3K4me3; hepatocytes; mitophagy; pyroptosis; septic-liver injury; trained immunity; zebrafish; β-glucan

DOI: https://doi.org/10.1016/j.celrep.2024.114324

Int Immunopharmacol. 2024 Jun 13. pii: S1567-5769(24)00902-0. [Epub ahead of print]137 112382

Primary infection enhances neutrophil-mediated host defense by educating HSPCs.

Peng Wu, Qingyu Zhang, Xianqun Xu, Songjiang He, Zheming Liu, Yirong Li, Rongxia Guo.

Hematopoietic stem and progenitor cells (HSPCs) can give rise to all kinds of immune cells including neutrophils. Neutrophils are the first line of defense in the innate immune system with a short lifespan, due to which it is well-accepted that neutrophils have no immune memory. However, recent reports showed that the changes in HSPCs induced by primary stimulation could last a long time, which contributes to enhancing response to subsequent infection by generating more monocytes or macrophages equipped with stronger anti-bacterial function. Here, we used the reinfection mice model to reveal that primary infection could improve neutrophil-mediated host defense by training neutrophil progenitors in mammals, providing a new idea to enhance neutrophil number and improve neutrophil functions, which is pretty pivotal for patients with compromised or disordered immunity.

Keywords: HSPCs; Host defense; Neutrophils; Reinfection

DOI: https://doi.org/10.1016/j.intimp.2024.112382

Inflamm Res. 2024 Jun 08.

Saccharomyces cerevisiae β-glucan improves the response of trained macrophages to severe P. aeruginosa infections.

Marta Ciszek-Lenda, Bernadeta Nowak, Grzegorz Majka, Maciej Suski, Maria Walczewska, Angelika Fedor, Edyta Golińska, Sabina Górska, Andrzej Gamian, Rafał Olszanecki, Magdalena Strus, Janusz Marcinkiewicz.

OBJECTIVE P. AERUGINOSA: (PA), the major pathogen of lung cystic fibrosis (CF), polarizes macrophages into hyperinflammatory tissue damaging phenotype. The main aim of this study was to verify whether training of macrophages with β-glucan might improve their response to P. aeruginosa infections.
METHODS: To perform this task C57BL/6 mice sensitive to infections with P. aeruginosa were used. Peritoneal macrophages were trained with Saccharomyces cerevisiae β-glucan and exposed to PA57, the strong biofilm-forming bacterial strain isolated from the patient with severe lung CF. The release of cytokines and the expression of macrophage phenotypic markers were measured. A quantitative proteomic approach was used for the characterization of proteome-wide changes in macrophages. The effect of in vivo β-glucan-trained macrophages in the air pouch model of PA57 infection was investigated. In all experiments the effect of trained and naïve macrophages was compared.
RESULTS: Trained macrophages acquired a specific phenotype with mixed pro-inflammatory and pro-resolution characteristics, however they retained anti-bacterial properties. Most importantly, transfer of trained macrophages into infected air pouches markedly ameliorated the course of infection. PA57 bacterial growth and formation of biofilm were significantly suppressed. The level of serum amyloid A (SAA), a systemic inflammation biomarker, was reduced.
CONCLUSIONS: Training of murine macrophages with S. cerevisiae β-glucan improved macrophage defense properties along with inhibition of secretion of some detrimental inflammatory agents. We suggest that training of macrophages with such β-glucans might be a new therapeutic strategy in P. aeruginosa biofilm infections, including CF, to promote eradication of pathogens and resolution of inflammation.

Keywords: Saccharomyces cerevisiae β-glucan; Biofilm P. Aeruginosa ; Inflammation; Trained macrophages

DOI: https://doi.org/10.1007/s00011-024-01898-1

bioRxiv. 2024 May 29. pii: 2024.05.28.595735. [Epub ahead of print]

A viral vaccine design harnessing prior BCG immunization confers protection against Ebola virus.

Tony W Ng, Wakako Furuyama, Ariel S Wirchnianski, Noemí A Saavedra-Ávila, Christopher T Johndrow, Kartik Chandran, William R Jacobs, Andrea Marzi, Steven A Porcelli.

Previous studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4 + helper T (Th) cells induced by Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination. This strategy uses immunization with recombinant fusion proteins comprised of a cell surface expressed viral antigen, such as a viral envelope glycoprotein, engineered to contain well-defined BCG Th cell epitopes, thus rapidly recruiting Th cells induced by prior BCG vaccination to provide intrastructural help to virus-specific B cells. In the current study, we show that Th cells induced by BCG were localized predominantly outside of germinal centers and promoted antibody class switching to isotypes characterized by strong Fc receptor interactions and effector functions. Furthermore, BCG vaccination also upregulated FcγR expression to potentially maximize antibody-dependent effector activities. Using a mouse model of Ebola virus (EBOV) infection, this vaccine strategy provided sustained antibody levels with strong IgG2c bias and protection against lethal challenge. This general approach can be easily adapted to other viruses, and may be a rapid and effective method of immunization against emerging pandemics in populations that routinely receive BCG vaccination.

DOI: https://doi.org/10.1101/2024.05.28.595735

Infect Immun. 2024 Jun 14. e0021624

Long-term changes in the phenotype and cytokine production of monocytes in COVID-19 recovered and vaccinated individuals.

Yekaterina O Ostapchuk, Anzhelika V Lushova, Sofia A Kan, Nurshat Abdolla, Aikyn Kali, Raikhan Tleulieva, Anastassiya V Perfilyeva, Yuliya V Perfilyeva.

Monocytes play a crucial role in the immune response against pathogens. Here, we sought to determine COVID-19 and the vaccine Gam-COVID-Vac induce long-term changes in the phenotype and cytokine production of circulating monocytes. Monocytes were purified from peripheral blood mononuclear cells of healthy donors who had not had COVID-19 or vaccination, who had received two doses of Gam-COVID-Vac, and who had mild/moderate COVID-19 in the last 6 months and evaluated by flow cytometry. To investigate the effect of SARS-CoV-2 proteins, monocytes were cultured for 2 days with or without stimulation with recombinant SARS-CoV-2 S1 and N peptides. Monocytes obtained from vaccinated and recovered individuals showed increased basal expression of HLA-DR, CD63, CXCR2, and TLR7. We also observed an increased frequency of CD63+ classical monocytes in both groups, as well as an increased frequency of HLA-DR+ non-classical monocytes in the COVID-19-recovered group compared to the control group. Monocytes from vaccinated and recovered donors produced higher basal levels of IL-6, IL-1β, and TNF-α cytokines. Ex vivo stimulation with SARS-CoV-2 antigens induced increased expression of HLA-DR and TLR7 on monocytes obtained from the control group. The challenge with SARS-CoV-2 antigens had no effect on the production of IL-6, IL-1β, and TNF-α cytokines by monocytes. The acquired data offer compelling evidence of enduring alterations in both the phenotype and functional status of circulating monocytes subsequent to vaccination with Gam-COVID-Vac and mild/moderate COVID-19 infection. At least some of these changes appear to be a consequence of exposure to SARS-CoV-2 S1 and N antigens.

Keywords: COVID-19; Gam-COVID-Vac vaccine; SARS-CoV-2 antigens; cytokines; monocytes; phenotype

DOI: https://doi.org/10.1128/iai.00216-24