bims-traimu Biomed News
on Trained immunity
Issue of 2022‒06‒26
five papers selected by
Yantong Wan
Southern Medical University

  1. J Clin Med. 2022 Jun 12. pii: 3369. [Epub ahead of print]11(12):
      Atherosclerosis remains the leading cause of cardiovascular diseases and represents a primary public health challenge. This chronic state may lead to a number of life-threatening conditions, such as myocardial infarction and stroke. Lipid metabolism alterations and inflammation remain at the forefront of the pathogenesis of atherosclerotic cardiovascular disease, but the overall mechanism is not yet fully understood. Recently, significant effects of trained immunity on atherosclerotic plaque formation and development have been reported. An increased reaction to restimulation with the same stimulator is a hallmark of the trained innate immune response. The impact of trained immunity is a prominent factor in both acute and chronic coronary syndrome, which we outline in this review.
    Keywords:  atherosclerosis; pathogenesis; trained immunity
  2. Vaccines (Basel). 2022 May 24. pii: 831. [Epub ahead of print]10(6):
      Tuberculosis (TB) is one of the top 10 leading causes of death worldwide. The recombinant BCG strain expressing the genetically detoxified A subunit of the thermolabile toxin from Escherichia coli (LTAK63) adjuvant (rBCG-LTAK63) has previously been shown to confer superior protection and immunogenicity compared to BCG in a murine TB infection model. To further investigate the immunological mechanisms induced by rBCG-LTAK63, we evaluated the immune responses induced by rBCG-LTAK63, BCG, and Mycobacterium tuberculosis (Mtb) H37Rv strains in experimental infections of primary human M1 and M2 macrophages at the transcriptomic and cytokine secretion levels. The rBCG-LTAK63-infected M1 macrophages more profoundly upregulated interferon-inducible genes such as IFIT3, OAS3, and antimicrobial gene CXCL9 compared to BCG, and induced higher levels of inflammatory cytokines such as IL-12(p70), TNF-β, and IL-15. The rBCG-LTAK63-infected M2 macrophages more extensively upregulated transcripts of inflammation-related genes, TAP1, GBP1, SLAMF7, TNIP1, and IL6, and induced higher levels of cytokines related to inflammation and tissue repair, MCP-3 and EGF, as compared to BCG. Thus, our data revealed an important signature of immune responses induced in human macrophages by rBCG-LTAK63 associated with increased inflammation, activation, and tissue repair, which may be correlated with a protective immune response against TB.
    Keywords:  BCG vaccination; cytokine profiling; gene expression profiling; immune response; primary human macrophages; recombinant BCG; tuberculosis
  3. Nat Rev Nephrol. 2022 Jun 20.
      Cellular hypoxia occurs when the demand for sufficient molecular oxygen needed to produce the levels of ATP required to perform physiological functions exceeds the vascular supply, thereby leading to a state of oxygen depletion with the associated risk of bioenergetic crisis. To protect against the threat of hypoxia, eukaryotic cells have evolved the capacity to elicit oxygen-sensitive adaptive transcriptional responses driven primarily (although not exclusively) by the hypoxia-inducible factor (HIF) pathway. In addition to the canonical regulation of HIF by oxygen-dependent hydroxylases, multiple other input signals, including gasotransmitters, non-coding RNAs, histone modifiers and post-translational modifications, modulate the nature of the HIF response in discreet cell types and contexts. Activation of HIF induces various effector pathways that mitigate the effects of hypoxia, including metabolic reprogramming and the production of erythropoietin. Drugs that target the HIF pathway to induce erythropoietin production are now approved for the treatment of chronic kidney disease-related anaemia. However, HIF-dependent changes in cell metabolism also have profound implications for functional responses in innate and adaptive immune cells, and thereby heavily influence immunity and the inflammatory response. Preclinical studies indicate a potential use of HIF therapeutics to treat inflammatory diseases, such as inflammatory bowel disease. Understanding the links between HIF, cellular metabolism and immunity is key to unlocking the full therapeutic potential of drugs that target the HIF pathway.
  4. Vaccines (Basel). 2022 Jun 14. pii: 945. [Epub ahead of print]10(6):
      Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the only approved vaccine against tuberculosis (TB). However, its efficacy in preventing pulmonary TB in adults is limited. Despite its variable efficacy, BCG offers a number of unique and beneficial characteristics, which make it suitable as a vaccine vehicle to express recombinant molecules. In Mycobacterium tuberculosis, the general Sec pathway is an essential cellular process, and it is responsible for exporting the majority of proteins across the cytoplasmic membrane, including potent immune-protective antigens, such as members of the antigen 85 (Ag85) complex. We engineered BCG to overexpress the M. tuberculosis SecDFG proteins in order to improve the efficiency of the Sec-dependent export system and, thus, enhance the secretion of immunogenic proteins. BCGSecDFG displayed increased intracellular survival within macrophages in vitro and greater persistence in the lymphoid organs of vaccinated mice than parental BCG. In addition, vaccination with BCGSecDFG generated higher numbers of IFN-γ-secreting T cells in response to secreted mycobacterial antigens compared to BCG, particularly members of the Ag85 complex. Furthermore, vaccination with BCGSecDFG significantly reduced the bacterial load in the lungs and spleens of M. tuberculosis-infected mice, which was comparable to the protection afforded by parental BCG. Therefore, the modification of protein secretion in BCG can improve antigen-specific immunogenicity.
    Keywords:  recombinant BCG; secretion system; tuberculosis; vaccines
  5. NPJ Vaccines. 2022 Jun 23. 7(1): 66
      Live attenuated vaccines often have beneficial non-specific effects, protecting against heterologous infectious and non-infectious diseases. We have developed a live attenuated pertussis vaccine, named BPZE1, currently in advanced clinical development. Here, we examined the prophylactic and therapeutic potential of its pertactin-deficient derivative BPZE1P in a mouse model of house dust mite (HDM)-induced allergic airway inflammation (AAI). BPZE1P was given nasally either before or after sensitization with HDM, followed by HDM challenge, or between two challenge episodes. Vaccination prior to sensitization reduced resistance in the airways, the numbers of infiltrating eosinophils and the concentrations of proinflammatory cytokines, such as IL-1α, IL-1β and IL-33, in the lungs but had no effect on Th2 cytokine levels. BPZE1P also protected when delivered after sensitization or between two challenge episodes. However, in this case the levels of Th2 cytokines in the lung were decreased without significant effects on IL-1α, IL-1β and IL-33 production. The vaccine restored lung function and decreased eosinophil influx in the lungs of HDM-treated mice. BPZE1P has a better take than BPZE1 in hosts vaccinated with acellular pertussis vaccines. Therefore, it has interesting potential as a preventive and therapeutic agent against AAI, even in acellular pertussis-vaccinated populations.