bims-traimu 2022-12-11 papers

bims-traimu

Biomed News

on Trained immunity

Issue of 2022–12–11
ten papers selected by
Yantong Wan, Southern Medical University

From trained immunity in allergy to trained immunity-based allergen vaccines.
The mechanisms and cross-protection of trained innate immunity.
Trained immunity can improve the disease resistance of red swamp crayfish (Procambarus clarkii).
Novel approaches to preventing phagosomal infections: timing is key.
Memory-like innate lymphoid cells in the pathogenesis of asthma.
Innate antiviral immunity and immunometabolism in hepatocytes.
Can bacterial lysates be useful in prevention of viral respiratory infections in childhood? The results of experimental OM-85 studies.
The adaptive immune system in early life: The shift makes it count.
The IRE1α-XBP1 Signaling Axis Promotes Glycolytic Reprogramming in Response to Inflammatory Stimuli.
Low-Dose Lipopolysaccharide Protects from Lethal Paramyxovirus Infection in a Macrophage- and TLR4-Dependent Process.

Clin Exp Allergy. 2022 Dec 09.

From trained immunity in allergy to trained immunity-based allergen vaccines.

Leticia Martín-Cruz, Carmen Sevilla-Ortega, Alba Angelina, Jorge Domínguez-Andrés, Mihai G Netea, José Luis Subiza, Oscar Palomares.

  Innate immune cells experience long lasting metabolic and epigenetic changes after an encounter with specific stimuli. This facilitates enhanced immune responses upon secondary exposition to both the same and unrelated pathogens, a process termed trained immunity. Trained immunity-based vaccines (TIbV) are vaccines able to induce innate immune memory, thus conferring heterologous protection against a broad range of pathogens. While trained immunity has been well documented in the context of infections and multiple immune-mediated diseases, the role of innate immune memory and its contribution to the initiation and maintenance of chronic allergic diseases remains poorly understood. Over the last years, different studies attempting to uncover the role of trained immunity in allergy have emerged. Exposition to environmental factors impacting allergy development such as allergens or viruses induces the reprogramming of innate immune cells to acquire a more pro-inflammatory phenotype in the context of asthma or food allergy. Several studies have convincingly demonstrated that prevention of viral infections using TIbV contributes to reduce wheezing attacks in children, which represent a high-risk factor for asthma development later in life. Innate immune cells trained with specific stimuli might also acquire anti-inflammatory features and promote tolerance, which may have important implications for chronic inflammatory diseases such as allergies. Recent findings showed that allergoid-mannan conjugates, which are next generation vaccines for allergen-specific immunotherapy (AIT), are able to reprogram monocytes into tolerogenic dendritic cells by mechanisms depending on metabolic and epigenetic rewiring. A better understanding of the underlying mechanisms of trained immunity in allergy will pave the way for the design of novel trained immunity-based allergen vaccines as potential alternative strategies for the prevention and treatment of allergic diseases.

Keywords:  allergy; asthma; basic immunology; clinical immunology; food allergy; innate immunity; trained immunity; trained immunity-based allergen vaccines

DOI:  https://doi.org/10.1111/cea.14261
Virol J. 2022 Dec 08. 19(1): 210

The mechanisms and cross-protection of trained innate immunity.

Shiwei Hu, Danhong Xiang, Xinlu Zhang, Lan Zhang, Shengjie Wang, Keyi Jin, Liangshun You, Jian Huang.

  In recent years, the traditional cognition of immunological memory being specific to adaptive immunity has been challenged. Innate immunity can mount enhanced responsiveness upon secondary stimulation, and a phenomenon is termed trained innate immunity. Trained innate immunity is orchestrated by distinct metabolic and epigenetic reprogramming in both circulating myeloid cells and myeloid progenitor cells in bone marrow, leading to long-term resistance to related and non-related pathogens infections. The induction of trained innate immunity can also polarize innate immune cells towards a hyperresponsive phenotype in the tumor microenvironment to exert antitumor effects. This review will discuss the current understanding of innate immune memory and the mechanisms during the induction of innate immunity, including signaling pathways, metabolic changes, and epigenetic rewriting. We also provide an overview of cross-protection against infectious diseases and cancers based on trained innate immunity.

Keywords:  Cancer; Cross-protection; Immune response; Infection; Mechanism; Trained innate immunity

DOI:  https://doi.org/10.1186/s12985-022-01937-5
Fish Shellfish Immunol. 2022 Dec 01. pii: S1050-4648(22)00801-4. [Epub ahead of print]132 108468

Trained immunity can improve the disease resistance of red swamp crayfish (Procambarus clarkii).

Xin Ren, Xiaoyu Liu, Xi Zhu, Lijing Xiong, Xufeng Bai.

  Trained immunity has been widely observed in mammals. Its identification in red swamp crayfish (Procambarus clarkii) is important for disease resistance in the crayfish farming industry. In this study, the mortality, expression of immune genes, production of reactive oxygen species (ROS), and phagocytosis ability of haemocytes in crayfish infected by pathogens (Vibrio parahaemolyticus or white spot syndrome virus) and crayfish trained with β-glucan or PBS (the control) were assessed when they were re-challenged by the pathogens. The results showed that the mortality of the trained and re-challenged crayfish were significantly lower than those of the untrained and challenged crayfish. Furthermore, the expression of immune genes, including Resistance (R), ALF, crustin2, and proPO, ROS levels, and phagocytosis ability of haemocytes, was significantly improved in the trained crayfish compared to that in the untrained crayfish. Interestingly, we found that the immune memory of trained crayfish lasted for at least 18 days. Together, these results indicate that crayfish develops trained immunity that can play an important role in the disease resistance. This suggests that trained immunity may be applied to improve disease resistance and crayfish production.

Keywords:  Disease resistance; Mortality; Red swamp crayfish (Procambarus clarkii); Trained immunity; β-glucan

DOI:  https://doi.org/10.1016/j.fsi.2022.108468
Trends Immunol. 2022 Dec 07. pii: S1471-4906(22)00239-3. [Epub ahead of print]

Novel approaches to preventing phagosomal infections: timing is key.

Nathan C Peters, Nargis Khan, Christopher H Mody.

  Prophylactic vaccination strategies designed to prevent diseases caused by pathogens using the phagolysosome of innate immune cells as a site of intracellular replication and survival have been largely ineffective. These include Mycobacterium tuberculosis (Mtb), Leishmania spp., and Cryptococcus spp. These failed strategies have traditionally targeted CD4+ T helper (Th) 1 cell-mediated immune memory, deeming it crucial for vaccine efficacy. This failure warrants an investigation of alternative mediators of protection. Here, we suggest three novel approaches to activate phagocytic cells prior to or at the time of infection. We hypothesize that preventing the formation of the pathogen niche within the phagolysosome is essential for preventing disease, and a greater emphasis on the timing of phagocyte activation should generate more effective prophylactic treatment options.

Keywords:  CD4 T helper 1 immunity; immune memory; intracellular infections; natural killer cells; phagolysosome; trained immunity; vaccination

DOI:  https://doi.org/10.1016/j.it.2022.11.004
Front Immunol. 2022 ;13 1005517

Memory-like innate lymphoid cells in the pathogenesis of asthma.

Jongho Ham, MinYeong Lim, Dongmo Kim, Hye Young Kim.

  Innate lymphoid cells (ILCs) are recently discovered innate immune cells that reside and self-renew in mucosal tissues and serve as the first line of defense against various external insults. They include natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer cells. The development and functions of ILC1-3 reflect those of their adaptive immunity TH1, TH2, and TH17 T-cell counterparts. Asthma is a heterogeneous disease caused by repeated exposure to specific allergens or host/environmental factors (e.g., obesity) that stimulate pathogenic pulmonary immune cells, including ILCs. Memory used to be a hallmark of adaptive immune cells until recent studies of monocytes, macrophages, and NK cells showed that innate immune cells can also exhibit greater responses to re-stimulation and that these more responsive cells can be long-lived. Besides, a series of studies suggest that the tissue-resident innate lymphoid cells have memory-like phenotypes, such as increased cytokine productions or epigenetic modifications following repetitive exposure to allergens. Notably, both clinical and mouse studies of asthma show that various allergens can generate memory-like features in ILC2s. Here, we discuss the biology of ILCs, their roles in asthma pathogenesis, and the evidence supporting ILC memory. We also show evidence suggesting memory ILCs could help drive the phenotypic heterogeneity in asthma. Thus, further research on memory ILCs may be fruitful in terms of developing new therapies for asthma.

Keywords:  asthma; epigenetic change; innate lymphoid cell; memory; trained immunity

DOI:  https://doi.org/10.3389/fimmu.2022.1005517
Curr Opin Immunol. 2022 Nov 29. pii: S0952-7915(22)00114-5. [Epub ahead of print]80 102267

Innate antiviral immunity and immunometabolism in hepatocytes.

Vasile Mihai Sularea, Jamie A Sugrue, Cliona O'Farrelly.

The human liver mediates whole-body metabolism, systemic inflammation and responses to hepatotropic pathogens. Hepatocytes, the most abundant cell type of the liver, have critical roles in each of these activities. The regulation of metabolic pathways, such as glucose metabolism, lipid biosynthesis and oxidation, influences whole-organism functionality. However, the immune potential of the liver in general and hepatocytes in particular is also determined by metabolic ability. The major shifts in cellular metabolism required to drive activity in immune cells are now well-described. Given the unique functions of hepatocytes in systemic metabolism and inflammation, and their ability to mediate local antiviral innate immunity, the metabolic shifts required to facilitate these activities are likely to be complex and challenging to define. In this review, we explore what is known about the complex metabolic rewiring required for hepatocytes to respond appropriately to viral infection. We also discuss how viruses can manipulate hepatocyte metabolism to facilitate infection.

DOI: https://doi.org/10.1016/j.coi.2022.102267
Front Pediatr. 2022 ;10 1051079

Can bacterial lysates be useful in prevention of viral respiratory infections in childhood? The results of experimental OM-85 studies.

Stefania Ballarini, Ledit Ardusso, José Antonio Ortega Martell, Oliviero Sacco, Wojciech Feleszko, Giovanni A Rossi.

  Respiratory tract infections (RTI) are mainly viral in origin and among the leading cause of childhood morbidity globally. Associated wheezing illness and asthma are still a clear unmet medical need. Despite the continuous progress in understanding the processes involved in their pathogenesis, preventive measures and treatments failed to demonstrate any significant disease-modifying effect. However, in the last decades it was understood that early-life exposure to microbes, may reduce the risk of infectious and allergic disorders, increasing the immune response efficacy. These results suggested that treatment with bacterial lysates (BLs) acting on gut microbiota, could promote a heterologous immunomodulation useful in the prevention of recurrent RTIs and of wheezing inception and persistence. This hypothesis has been supported by clinical and experimental studies showing the reduction of RTI frequency and severity in childhood after oral BL prophylaxis and elucidating the involved mechanisms. OM-85 is the product whose anti-viral effects have been most extensively studied in vitro, animal, and human cell studies and in translational animal infection/disease models. The results of the latter studies, describing the potential immune training-based activities of such BL, leading to the protection against respiratory viruses, will be reported. In response to human rhinovirus, influenza virus, respiratory syncytial virus and severe acute respiratory coronavirus-2, OM-85 was effective in modulating the structure and the functions of a large numbers of airways epithelial and immune cells, when administered both orally and intranasally.

Keywords:  HRV; IFV; OM-85; RSV; SARS-CoV-2; bacterial lysates; respiratory infections; trained immunity

DOI:  https://doi.org/10.3389/fped.2022.1051079
Front Immunol. 2022 ;13 1031924

The adaptive immune system in early life: The shift makes it count.

Daan K J Pieren, Mardi C Boer, Jelle de Wit.

  Respiratory infectious diseases encountered early in life may result in life-threatening disease in neonates, which is primarily explained by the relatively naive neonatal immune system. Whereas vaccines are not readily available for all infectious diseases, vaccinations have greatly reduced childhood mortality. However, repeated vaccinations are required to reach protective immunity in infants and not all vaccinations are effective at young age. Moreover, protective adaptive immunity elicited by vaccination wanes more rapidly at young age compared to adulthood. The infant adaptive immune system has previously been considered immature but this paradigm has changed during the past years. Recent evidence shows that the early life adaptive immune system is equipped with a strong innate-like effector function to eliminate acute pathogenic threats. These strong innate-like effector capacities are in turn kept in check by a tolerogenic counterpart of the adaptive system that may have evolved to maintain balance and to reduce collateral damage. In this review, we provide insight into these aspects of the early life's adaptive immune system by addressing recent literature. Moreover, we speculate that this shift from innate-like and tolerogenic adaptive immune features towards formation of immune memory may underlie different efficacy of infant vaccination in these different phases of immune development. Therefore, presence of innate-like and tolerogenic features of the adaptive immune system may be used as a biomarker to improve vaccination strategies against respiratory and other infections in early life.

Keywords:  adaptive immune system; biomarker; heterogeneity; immune memory; infants; respiratory infectious diseases; tolerance; vaccination

DOI:  https://doi.org/10.3389/fimmu.2022.1031924
mBio. 2022 Dec 08. e0306822

The IRE1α-XBP1 Signaling Axis Promotes Glycolytic Reprogramming in Response to Inflammatory Stimuli.

Bevin C English, Hannah P Savage, Scott P Mahan, Vladimir E Diaz-Ochoa, Briana M Young, Basel H Abuaita, Gautam Sule, Jason S Knight, Mary X O'Riordan, Andreas J Bäumler, Renée M Tsolis.

  Immune cells must be able to adjust their metabolic programs to effectively carry out their effector functions. Here, we show that the endoplasmic reticulum (ER) stress sensor Inositol-requiring enzyme 1 alpha (IRE1α) and its downstream transcription factor X box binding protein 1 (XBP1) enhance the upregulation of glycolysis in classically activated macrophages (CAMs). The IRE1α-XBP1 signaling axis supports this glycolytic switch in macrophages when activated by lipopolysaccharide (LPS) stimulation or infection with the intracellular bacterial pathogen Brucella abortus. Importantly, these different inflammatory stimuli have distinct mechanisms of IRE1α activation; while Toll-like receptor 4 (TLR4) supports glycolysis under both conditions, TLR4 is required for activation of IRE1α in response to LPS treatment but not B. abortus infection. Though IRE1α and XBP1 are necessary for maximal induction of glycolysis in CAMs, activation of this pathway is not sufficient to increase the glycolytic rate of macrophages, indicating that the cellular context in which this pathway is activated ultimately dictates the cell's metabolic response and that IRE1α activation may be a way to fine-tune metabolic reprogramming. IMPORTANCE The immune system must be able to tailor its response to different types of pathogens in order to eliminate them and protect the host. When confronted with bacterial pathogens, macrophages, frontline defenders in the immune system, switch to a glycolysis-driven metabolism to carry out their antibacterial functions. Here, we show that IRE1α, a sensor of ER stress, and its downstream transcription factor XBP1 support glycolysis in macrophages during infection with Brucella abortus or challenge with Salmonella LPS. Interestingly, these stimuli activate IRE1α by independent mechanisms. While the IRE1α-XBP1 signaling axis promotes the glycolytic switch, activation of this pathway is not sufficient to increase glycolysis in macrophages. This study furthers our understanding of the pathways that drive macrophage immunometabolism and highlights a new role for IRE1α and XBP1 in innate immunity.

Keywords:  Brucella; endoplasmic reticulum; immunometabolism; innate immunity

DOI:  https://doi.org/10.1128/mbio.03068-22
J Immunol. 2022 Dec 07. pii: ji2200604. [Epub ahead of print]

Low-Dose Lipopolysaccharide Protects from Lethal Paramyxovirus Infection in a Macrophage- and TLR4-Dependent Process.

Jenny Resiliac, Michelle Rohlfing, Jennifer Santoro, Syed-Rehan A Hussain, Mitchell H Grayson.

Respiratory diseases are a major public health burden and a leading cause of death and disability in the world. Understanding antiviral immune responses is crucial to alleviate morbidity and mortality associated with these respiratory viral infections. Previous data from human and animal studies suggested that pre-existing atopy may provide some protection against severe disease from a respiratory viral infection. However, the mechanism(s) of protection is not understood. Low-dose LPS has been shown to drive an atopic phenotype in mice. In addition, LPS has been shown in vitro to have an antiviral effect. We examined the effect of LPS treatment on mortality to the murine parainfluenza virus Sendai virus. Low-dose LPS treatment 24 h before inoculation with a normally lethal dose of Sendai virus greatly reduced death. This protection was associated with a reduced viral titer and reduced inflammatory cytokine production in the airways. The administration of LPS was associated with a marked increase in lung neutrophils and macrophages. Depletion of neutrophils failed to reverse the protective effect of LPS; however, depletion of macrophages reversed the protective effect of LPS. Further, we demonstrate that the protective effect of LPS depends on type I IFN and TLR4-MyD88 signaling. Together, these studies demonstrate pretreatment with low-dose LPS provides a survival advantage against a severe respiratory viral infection through a macrophage-, TLR4-, and MyD88-dependent pathway.

DOI: https://doi.org/10.4049/jimmunol.2200604