bims-traimu 2023-06-04 papers

Issue of 2023–06–04
four papers selected by
Yantong Wan, Southern Medical University

J Mol Biol. 2023 May 30. pii: S0022-2836(23)00256-5. [Epub ahead of print] 168169

BCG-induced trained immunity and emergency granulopoiesis in pathogen agnostic effects of the vaccine.

Henok Andualem, Elysia Hollams, Tobias R Kollmann, Nelly Amenyogbe.

Bacille Calmette-Guérin (BCG) is the most commonly administered vaccine in human history. The medical application of BCG extends far beyond the fight against tuberculosis. Despite its stellar medical record over 100 years, insight into how BCG provides this vast range of benefits is surprisingly limited, both for its pathogen-specific (tuberculosis) as well as pathogen-agnostic (other infections, autoimmunity, allergies, and cancer) effects. Trained immunity and emergency granulopoiesis have been identified as mediating BCG's pathogen-agnostic effects, for which some of the molecular mechanisms have been delineated. Upon review of the existing evidence, we postulate that emergency granulopoiesis and trained immunity are a continuum of the same effect cascade. In this context, we highlight that BCG's pathogen-agnostic benefits could be optimized by taking advantage of the age of the recipient and route of BCG administration.

Keywords: BCG; Emergency granulopoiesis; Mechanism; Modulators; Trained Immunity

DOI: https://doi.org/10.1016/j.jmb.2023.168169

iScience. 2023 Jun 16. 26(6): 106873

Mycobacterium manresensis induces trained immunity in vitro.

The COVID-19 pandemic posed a global health crisis, with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants weakening vaccine-driven protection. Trained immunity could help tackle COVID-19 disease. Our objective was to analyze whether heat-killed Mycobacterium manresensis (hkMm), an environmental mycobacterium, induces trained immunity and confers protection against SARS-CoV-2 infection. To this end, THP-1 cells and primary monocytes were trained with hkMm. The increased secretion of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, and IL-10, metabolic activity, and changes in epigenetic marks suggested hkMm-induced trained immunity in vitro. Healthcare workers at risk of SARS-CoV-2 infection were enrolled into the MANRECOVID19 clinical trial (NCT04452773) and were administered Nyaditum resae (NR, containing hkMm) or placebo. No significant differences in monocyte inflammatory responses or the incidence of SARS-CoV-2 infection were found between the groups, although NR modified the profile of circulating immune cell populations. Our results show that M. manresensis induces trained immunity in vitro but not in vivo when orally administered as NR daily for 14 days.

Keywords: Biological sciences; Immunology; Microbiology; Molecular biology

DOI: https://doi.org/10.1016/j.isci.2023.106873

Curr Cardiol Rep. 2023 May 30.

The Role of Innate Immune Cells in Cardiac Injury and Repair: A Metabolic Perspective.

Durba Banerjee, Rong Tian, Shanshan Cai.

PURPOSE OF REVIEW: Recent technological advances have identified distinct subpopulations and roles of the cardiac innate immune cells, specifically macrophages and neutrophils. Studies on distinct metabolic pathways of macrophage and neutrophil in cardiac injury are expanding. Here, we elaborate on the roles of cardiac macrophages and neutrophils in concomitance with their metabolism in normal and diseased hearts.
RECENT FINDINGS: Single-cell techniques combined with fate mapping have identified the clusters of innate immune cell subpopulations present in the resting and diseased hearts. We are beginning to know about the presence of cardiac resident macrophages and their functions. Resident macrophages perform cardiac homeostatic roles, whereas infiltrating neutrophils and macrophages contribute to tissue damage during cardiac injury with eventual role in repair. Prior studies show that metabolic pathways regulate the phenotypes of the macrophages and neutrophils during cardiac injury. Profiling the metabolism of the innate immune cells, especially of resident macrophages during chronic and acute cardiac diseases, can further the understanding of cardiac immunometabolism.

Keywords: Cardiac homeostasis; Cardiac injury; Immunometabolism; Inflammation; Macrophage; Neutrophil

DOI: https://doi.org/10.1007/s11886-023-01897-4

Curr Pharm Des. 2023 May 30.

ZNF667 Suppressed LPS-induced Macrophages Inflammation through mTORdependent Aerobic Glycolysis Regulation.

Yongzhen Li, Ru Chao, Shun-Lin Qu, Liang Huang, Chi Zhang.

BACKGROUND: Macrophages participate in all stages of the inflammatory response, and the excessive release of inflammatory mediators and other cytokines synthesized and secreted by macrophages is fundamentally linked to an uncontrolled inflammatory response. The zinc finger 667 (ZNF667) protein, a novel DNAbinding protein, has been shown to play a vital role in oxidative stress. However, none of the target genes in macrophages or the potential roles of ZNF667 have been elucidated to date.
OBJECTIVES: The present study was designed to investigate the effects of ZNF667 on LPS-induced inflammation in macrophages.
METHODS: The RAW264.7 macrophage cell line was selected as a model system. Inflammatory response-related gene expression levels and phosphorylation levels of PI3K, AKT, and mTOR were detected in LPS-treated macrophages via RT-PCR and western blotting, respectively.
RESULTS: We found that LPS resulted in the up-regulation of ZNF667 in macrophages and a peak response in ZNF667 protein expression levels when used at a concentration of 100 ng/mL. ZNF667 overexpression significantly inhibited the LPS-induced up-regulation of iNOS, and IL-1β mRNA and protein expression levels, together with the secretion of IL-1β, IL-6, and TNF-α. ZNF667 overexpression also inhibited PI3K, AKT, and mTOR hyperphosphorylation and had no effect on the phosphorylation of NF-κB p65, ERK1/2, MAPK p38, and the transcriptional activity of NF-κB in macrophages. The up-regulation of ZNF667 inhibited the levels of expression of HK2 and PFKFB3, glucose consumption, and lactate production in LPS-stimulated macrophages. The up-regulation of mRNA levels of LPS-induced glycolytic genes HK2 and PFKFB3 and the increased mRNA expression of pro-inflammatory cytokines (IL-1β and iNOS) were abolished by hexokinase inhibitor 2-DG in ZNF667-deficient macrophages. Meanwhile, glucose consumption and lactate production were abrogated in macrophages when cells were treated with the specific mTOR inhibitor RPM.
CONCLUSION: Our results demonstrate that ZNF667 suppressed LPS-stimulated RAW264.7 macrophage inflammation by regulating mTOR-dependent aerobic glycolysis.

Keywords: aerobic glycolysis; inflammation; lipopolysaccharide; macrophages; mammalian target of rapamycin; zinc finger protein 667

DOI: https://doi.org/10.2174/1381612829666230530143129