bims-traimu 2023-05-28 papers

Issue of 2023–05–28
four papers selected by
Yantong Wan, Southern Medical University

Viruses. 2023 May 19. pii: 1204. [Epub ahead of print]15(5):

β-Glucan Induces Training Immunity to Promote Antiviral Activity by Activating TBK1.

Guolei Wang, Zhiqiang Li, Mingfu Tian, Xianghua Cui, Jun'e Ma, Siyu Liu, Chenglin Ye, Li Yuan, Muhammad Suhaib Qudus, Uzair Afaq, Kailang Wu, Xinghui Liu, Chengliang Zhu.

Many studies have shown that β-glucan induces a trained immune phenotype in innate immune cells to defend against bacterial and fungal infections. The specific mechanism involves cellular metabolism and epigenetic reprogramming. However, it is unclear whether β-glucan plays a role in antiviral infection. Therefore, this study investigated the role of trained immunity induced by Candida albicans and β-glucan in antiviral innate immunity. It showed that C. albicans and β-glucan promoted the expression of interferon-β (IFN-β) and interleukin-6 (IL-6) in mouse macrophages triggered by viral infection. In addition, β-glucan pretreatment attenuated the pathological damage induced by the virus in mouse lungs and promoted the expression of IFN-β. Mechanistically, β-glucan could promote the phosphorylation and ubiquitination of TANK Binding Kinase 1 (TBK1), a key protein of the innate immune pathway. These results suggest that β-glucan can promote innate antiviral immunity, and this bioactive material may be a potential therapeutic target for antiviral treatment.

Keywords: TBK1; innate immunity; trained immunity; ubiquitination

DOI: https://doi.org/10.3390/v15051204

Biomedicines. 2023 Apr 23. pii: 1245. [Epub ahead of print]11(5):

Metallic Nanoparticles: Their Potential Role in Breast Cancer Immunotherapy via Trained Immunity Provocation.

Elham Zarenezhad, Manal Hadi Ghaffoori Kanaan, Sura Saad Abdollah, Mohammad Kazem Vakil, Mahrokh Marzi, Abdulbaset Mazarzaei, Abdolmajid Ghasemian.

Owing to drawbacks in the current common cancer therapies including surgery, chemotherapy and radiotherapy, the development of more reliable, low toxic, cost-effective and specific approaches such as immunotherapy is crucial. Breast cancer is among the leading causes of morbidity and mortality with a developed anticancer resistance. Accordingly, we attempted to uncover the efficacy of metallic nanoparticles (MNPs)-based breast cancer immunotherapy emphasizing trained immunity provocation or innate immunity adaptation. Due to the immunosuppressive nature of the tumor microenvironment (TME) and the poor infiltration of immune cells, the potentiation of an immune response or direct combat is a goal employing NPs as a burgeoning field. During the recent decades, the adaptation of the innate immunity responses against infectious diseases and cancer has been recognized. Although the data is in a scarcity with regard to a trained immunity function in breast cancer cells' elimination, this study introduced the potential of this arm of immunity adaptation using MNPs.

Keywords: breast cancer; cancer therapy; drug delivery; nanoparticles; trained immunity

DOI: https://doi.org/10.3390/biomedicines11051245

Int J Mol Sci. 2023 May 18. pii: 8967. [Epub ahead of print]24(10):

Modelling Microglial Innate Immune Memory In Vitro: Understanding the Role of Aerobic Glycolysis in Innate Immune Memory.

Morgan Towriss, Brian MacVicar, Annie Vogel Ciernia.

Microglia, the resident macrophages of the central nervous system, play important roles in maintaining brain homeostasis and facilitating the brain's innate immune responses. Following immune challenges microglia also retain immune memories, which can alter responses to secondary inflammatory challenges. Microglia have two main memory states, training and tolerance, which are associated with increased and attenuated expression of inflammatory cytokines, respectively. However, the mechanisms differentiating these two distinct states are not well understood. We investigated mechanisms underlying training versus tolerance memory paradigms in vitro in BV2 cells using B-cell-activating factor (BAFF) or bacterial lipopolysaccharide (LPS) as a priming stimulus followed by LPS as a second stimulus. BAFF followed by LPS showed enhanced responses indicative of priming, whereas LPS followed by LPS as the second stimulus caused reduced responses suggestive of tolerance. The main difference between the BAFF versus the LPS stimulus was the induction of aerobic glycolysis by LPS. Inhibiting aerobic glycolysis during the priming stimulus using sodium oxamate prevented the establishment of the tolerized memory state. In addition, tolerized microglia were unable to induce aerobic glycolysis upon LPS restimulus. Therefore, we conclude that aerobic glycolysis triggered by the first LPS stimulus was a critical step in the induction of innate immune tolerance.

Keywords: BV2; DOHaD; innate immune memory; metabolism; microglia; tolerance; training

DOI: https://doi.org/10.3390/ijms24108967

FASEB J. 2023 Jun;37(6): e22951

Single-cell transcriptome profiling reveals diverse immune cell populations and their responses to viral infection in the spleen of zebrafish.

Chong-Bin Hu, Jie Wang, Yun Hong, Hao Li, Dong-Dong Fan, Ai-Fu Lin, Li-Xin Xiang, Jian-Zhong Shao.

Teleost fish are indispensable model organisms for comparative immunology research that should lead to an improved understanding of the general principles of vertebrate immune system design. Although numerous studies on fish immunology have been conducted, knowledge about the cell types that orchestrate piscine immune systems remains limited. Here, we generated a comprehensive atlas of immune cell types in zebrafish spleen on the basis of single-cell transcriptome profiling. We identified 11 major categories from splenic leukocyte preparations, including neutrophils, natural killer cells, macrophages/myeloid cells, T cells, B cells, hematopoietic stem and progenitor cells, mast cells, remnants of endothelial cells, erythroid cells, erythroid progenitors, and a new type of serpin-secreting cells. Notably, we derived 54 potential subsets from these 11 categories. These subsets showed differential responses to spring viremia of carp virus (SVCV) infection, implying that they have diverse roles in antiviral immunity. Additionally, we landscaped the populations with the induced expression of interferons and other virus-responsive genes. We found that trained immunity can be effectively induced in the neutrophil and M1-macrophage subsets by vaccinating zebrafish with inactivated SVCV. Our findings illustrated the complexity and heterogeneity of the fish immune system, which will help establish a new paradigm for the improved understanding of fish immunology.

Keywords: antiviral immunity; atlas of immune cells; heterogeneity of fish immune cells; single-cell transcriptome profiling; trained immunity; zebrafish

DOI: https://doi.org/10.1096/fj.202201505RRRR