bims-traimu Biomed News
on Trained immunity
Issue of 2023–07–16
ten papers selected by
Yantong Wan, Southern Medical University
  1. Roles of trained immunity in the pathogenesis of periodontitis.
  2. No evidence for trans-generational immune priming in Drosophila melanogaster.
  3. Intranasal influenza-vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response in hamsters.
  4. BCG to Protect against Covid-19 in Health Care Workers.
  5. Turning foes into permissive hosts: manipulation of macrophage polarization by intracellular bacteria.
  6. Memory-like innate response to booster vaccination with MF-59 adjuvanted influenza vaccine in children.
  7. GSDMD in peripheral myeloid cells regulates microglial immune training and neuroinflammation in Parkinson's disease.
  8. Lipopolysaccharide augments microglial GABA uptake by increasing GABA transporter-1 trafficking and bestrophin-1 expression.
  9. Protective antigen of Bacillus anthracis in combination with TLR4 or TLR5 agonist confers superior protection against lethal challenge in mouse model.
  10. YF17D-vectored Ebola vaccine candidate protects mice against lethal surrogate Ebola and yellow fever virus challenge.
  1. J Periodontal Res. 2023 Jul 09.
    Roles of trained immunity in the pathogenesis of periodontitis.
    Yingyi Li, Yue Chen, Guanhui Cai, Qiaoqi Ni, Ying Geng, Ting Wang, Chen Bao, Xiaolei Ruan, Hua Wang, Wen Sun.
      Periodontitis is a chronic, inflammatory, and destructive disease caused by the imbalance of host immune response and dental biofilm, and has strong epidemiological and pathogenesis correlations with systemic diseases. The immune response in periodontitis involves both innate and adaptive immunity, with numerous immune cells and inflammatory pathways participating in a complex network of interactions. In the past decade, the concept of "trained immunity" has emerged, which highlights the memory characteristics of innate immunity, thus opening up a new avenue of research. There is growing interest in exploring the role of trained immunity in chronic inflammatory and metabolic diseases such as atherosclerosis and diabetes mellitus. Evidence suggests that trained immunity may also regulate the onset and progression of periodontitis, serving as a bridge between periodontitis-related comorbidities. In this review, we summarize concepts related to trained immunity and its development. Furthermore, we present current evidence that endorses the notion of trained immunity in periodontitis and analyze possible roles it may assume regarding periodontitis-associated inflammatory reactions from a cellular perspective. Finally, we discuss various clinical therapeutic strategies for periodontitis and its associated comorbidities that target trained immunity. We hope that more researchers will pay attention to this emerging concept, thereby providing deeper insights into this novel field.
    Keywords:  inflammation; innate immune cells; periodontitis; trained immunity
    DOI:  https://doi.org/10.1111/jre.13158
  2. PLoS One. 2023 ;18(7): e0288342
    No evidence for trans-generational immune priming in Drosophila melanogaster.
    R Radhika, Brian P Lazzaro.
      Most organisms are under constant and repeated exposure to pathogens, leading to perpetual natural selection for more effective ways to fight-off infections. This could include the evolution of memory-based immunity to increase protection from repeatedly-encountered pathogens both within and across generations. There is mixed evidence for intra- and trans-generational priming in non-vertebrates, which lack the antibody-mediated acquired immunity characteristic of vertebrates. In this work, we tested for trans-generational immune priming in adult offspring of the fruit fly, Drosophila melanogaster, after maternal challenge with 10 different bacterial pathogens. We focused on natural opportunistic pathogens of Drosophila spanning a range of virulence from 10% to 100% host mortality. We infected mothers via septic injury and tested for enhanced resistance to infection in their adult offspring, measured as the ability to suppress bacterial proliferation and survive infection. We categorized the mothers into four classes for each bacterium tested: those that survived infection, those that succumbed to infection, sterile-injury controls, and uninjured controls. We found no evidence for trans-generational priming by any class of mother in response to any of the bacteria.
    DOI:  https://doi.org/10.1371/journal.pone.0288342
  3. Nat Commun. 2023 07 11. 14(1): 4117
    Intranasal influenza-vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response in hamsters.
    Liang Zhang, Yao Jiang, Jinhang He, Junyu Chen, Ruoyao Qi, Lunzhi Yuan, Tiange Shao, Hui Zhao, Congjie Chen, Yaode Chen, Xijing Wang, Xing Lei, Qingxiang Gao, Chunlan Zhuang, Ming Zhou, Jian Ma, Wei Liu, Man Yang, Rao Fu, Yangtao Wu, Feng Chen, Hualong Xiong, Meifeng Nie, Yiyi Chen, Kun Wu, Mujin Fang, Yingbin Wang, Zizheng Zheng, Shoujie Huang, Shengxiang Ge, Shih Chin Cheng, Huachen Zhu, Tong Cheng, Quan Yuan, Ting Wu, Jun Zhang, Yixin Chen, Tianying Zhang, Changgui Li, Hai Qi, Yi Guan, Ningshao Xia.
      The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and "anatomical escape" characteristics threaten the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. Here we investigate immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants in hamsters. Intranasal delivery of dNS1-RBD induces innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrains the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (Il6, Il1b, and Ifng) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.
    DOI:  https://doi.org/10.1038/s41467-023-39560-9
  4. N Engl J Med. 2023 Jul 13. pii: 10.1056/NEJMc2306483#sa2. [Epub ahead of print]389(2): 191-192
    BCG to Protect against Covid-19 in Health Care Workers.
    Christine S Benn, Mihai G Netea, Peter Aaby.
      
    DOI:  https://doi.org/10.1056/NEJMc2306483
  5. Curr Opin Immunol. 2023 Jul 10. pii: S0952-7915(23)00086-9. [Epub ahead of print]84 102367
    Turning foes into permissive hosts: manipulation of macrophage polarization by intracellular bacteria.
    Trung Hm Pham, Denise M Monack.
      Macrophages function as tissue-immune sentinels and mediate key antimicrobial responses against bacterial pathogens. Yet, they can also act as a cellular niche for intracellular bacteria, such as Salmonella enterica, to persist in infected tissues. Macrophages exhibit heterogeneous activation or polarization, states that are linked to differential antibacterial responses and bacteria permissiveness. Remarkably, recent studies demonstrate that Salmonella and other intracellular bacteria inject virulence effectors into the cellular cytoplasm to skew the macrophage polarization state and reprogram these immune cells into a permissive niche. Here, we review mechanisms of macrophage reprogramming by Salmonella and highlight manipulation of macrophage polarization as a shared bacterial pathogenesis strategy. In addition, we discuss how the interplay of bacterial effector mechanisms, microenvironmental signals, and ontogeny may shape macrophage cell states and functions. Finally, we propose ideas of how further research will advance our understanding of macrophage functional diversity and immunobiology.
    DOI:  https://doi.org/10.1016/j.coi.2023.102367
  6. NPJ Vaccines. 2023 Jul 13. 8(1): 100
    Memory-like innate response to booster vaccination with MF-59 adjuvanted influenza vaccine in children.
    Dmitri Kazmin, Elizabeth A Clutterbuck, Giorgio Napolitani, Amanda L Wilkins, Andrea Tarlton, Amber J Thompson, Emmanuele Montomoli, Guilia Lapini, Smiti Bihari, Rachel White, Claire Jones, Matthew D Snape, Ushma Galal, Ly-Mee Yu, Rino Rappuoli, Giuseppe Del Giudice, Andrew J Pollard, Bali Pulendran.
      The pediatric population receives the majority of vaccines globally, yet there is a paucity of studies on the transcriptional response induced by immunization in this special population. In this study, we performed a systems-level analysis of immune responses to the trivalent inactivated influenza vaccine adjuvanted with MF-59 in children (15-24 months old) and in young, healthy adults. We analyzed transcriptional responses elicited by vaccination in peripheral blood, as well as cellular and antibody responses following primary and booster vaccinations. Our analysis revealed that primary vaccination induced a persistent transcriptional signature of innate immunity; booster vaccination induced a transcriptional signature of an enhanced memory-like innate response, which was consistent with enhanced activation of myeloid cells assessed by flow cytometry. Furthermore, we identified a transcriptional signature of type 1 interferon response post-booster vaccination and at baseline that was correlated with the local reactogenicity to vaccination and defined an early signature that correlated with the hemagglutinin antibody titers. These results highlight an adaptive behavior of the innate immune system in evoking a memory-like response to secondary vaccination and define molecular correlates of reactogenicity and immunogenicity in infants.
    DOI:  https://doi.org/10.1038/s41541-023-00702-1
  7. Acta Pharm Sin B. 2023 Jun;13(6): 2663-2679
    GSDMD in peripheral myeloid cells regulates microglial immune training and neuroinflammation in Parkinson's disease.
    Bingwei Wang, Yan Ma, Sheng Li, Hang Yao, Mingna Gu, Ying Liu, You Xue, Jianhua Ding, Chunmei Ma, Shuo Yang, Gang Hu.
      Peripheral bacterial infections without impaired blood-brain barrier integrity have been attributed to the pathogenesis of Parkinson's disease (PD). Peripheral infection promotes innate immune training in microglia and exacerbates neuroinflammation. However, how changes in the peripheral environment mediate microglial training and exacerbation of infection-related PD is unknown. In this study, we demonstrate that GSDMD activation was enhanced in the spleen but not in the CNS of mice primed with low-dose LPS. GSDMD in peripheral myeloid cells promoted microglial immune training, thus exacerbating neuroinflammation and neurodegeneration during PD in an IL-1R-dependent manner. Furthermore, pharmacological inhibition of GSDMD alleviated the symptoms of PD in experimental PD models. Collectively, these findings demonstrate that GSDMD-induced pyroptosis in myeloid cells initiates neuroinflammation by regulating microglial training during infection-related PD. Based on these findings, GSDMD may serve as a therapeutic target for patients with PD.
    Keywords:  GSDMD; Immune training; Neuroinflammation; Parkinson's disease
    DOI:  https://doi.org/10.1016/j.apsb.2023.04.008
  8. Glia. 2023 Jul 10.
    Lipopolysaccharide augments microglial GABA uptake by increasing GABA transporter-1 trafficking and bestrophin-1 expression.
    Michael Di Palma, Myriam Catalano, Carmela Serpe, Mariassunta De Luca, Lucia Monaco, Karl Kunzelmann, Cristina Limatola, Fiorenzo Conti, Giorgia Fattorini.
      Gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the brain, affects numerous immune cell functions. Microglia, the brain's resident innate immune cells, regulate GABA signaling through GABA receptors and express the complete GABAergic machinery for GABA synthesis, uptake, and release. Here, the use of primary microglial cell cultures and ex vivo brain tissue sections allowed for demonstrating that treatment with lipopolysaccharide (LPS) increased microglial GABA uptake as well as GABA transporter (GAT)-1 trafficking. This effect was not entirely abolished by treatment with GAT inhibitors (GAT-Is). Notably, LPS also induced microglial upregulation of bestrophin-1 (BEST-1), a Ca2+ -activated Cl- channel permeable to GABA. Combined administration of GAT-Is and a BEST-1 inhibitor completely abolished LPS-induced microglial GABA uptake. Interestingly, increased microglial GAT-1 membrane turnover via syntaxin 1A was detected in LPS-treated cultures after BEST-1 blockade. Altogether, these findings provided evidence for a novel mechanism through which LPS may trigger the inflammatory response by directly altering microglial GABA clearance and identified the GAT-1/BEST-1 interplay as a potential novel mechanism involved in brain inflammation.
    Keywords:  GABA; GABA transporter 1; LPS; bestrophin-1; inflammation; microglial cells
    DOI:  https://doi.org/10.1002/glia.24437
  9. Microbes Infect. 2023 Jul 10. pii: S1286-4579(23)00086-2. [Epub ahead of print] 105183
    Protective antigen of Bacillus anthracis in combination with TLR4 or TLR5 agonist confers superior protection against lethal challenge in mouse model.
    Bineet Narayan, Shailendra Kumar Verma, Sandeep Singh, Mahendra K Gupta, Subodh Kumar.
      The immunogenicity and protective ability of recombinant PA (rPA) with two innate immune system modulators, i.e., monophosphoryl lipid A (MPLA), a TLR4 agonist, and recombinant flagellin C (FliC), a TLR5 agonist, were studied in the mouse model. BALB/c mice were inoculated with three doses of rPA+alum (Alum group), rPA+FliC+alum (FliC group), rPA+MPLA+alum (MPLA group), or only alum adjuvant (Alum alone group). Significant increases in anti-PA IgG titers were observed in the Alum, FliC and MPLA groups when compared to control Alum alone group. Similarly, a significant enhancement of proinflammatory (TNF-α, IL-1β), Th1 (IFN-γ, IL-12(p70), IL-2) and Th2 (IL-10, IL-4) cytokines were also noticed in Alum, FliC and MPLA groups compared to Alum alone group. The rPA-specific IgG and cytokine responses in MPLA and FliC groups were significantly higher than the Alum group, suggesting enhancement of immune response by these TLR agonists. MPLA was also found to skew the IgG1:IgG2a ratio towards IgG2a. At a challenge dose of 25 LD50, complete protection was observed in mice of MPLA group whereas lesser protection was observed in FliC (80%) and Alum (50%) groups. Therefore, we suggest the use of MPLA in further development of rPA based anthrax vaccines.
    Keywords:  Anthrax; Bacillus anthracis; Flagellin; Monophosphoryl Lipid A; Protective antigen; Vaccine
    DOI:  https://doi.org/10.1016/j.micinf.2023.105183
  10. NPJ Vaccines. 2023 Jul 11. 8(1): 99
    YF17D-vectored Ebola vaccine candidate protects mice against lethal surrogate Ebola and yellow fever virus challenge.
    Viktor Lemmens, Lara Kelchtermans, Sarah Debaveye, Winston Chiu, Thomas Vercruysse, Ji Ma, Hendrik Jan Thibaut, Johan Neyts, Lorena Sanchez-Felipe, Kai Dallmeier.
      Ebola virus (EBOV) and related filoviruses such as Sudan virus (SUDV) threaten global public health. Effective filovirus vaccines are available only for EBOV, yet restricted to emergency use considering a high reactogenicity and demanding logistics. Here we present YF-EBO, a live YF17D-vectored dual-target vaccine candidate expressing EBOV glycoprotein (GP) as protective antigen. Safety of YF-EBO in mice was further improved over that of parental YF17D vaccine. A single dose of YF-EBO was sufficient to induce high levels of EBOV GP-specific antibodies and cellular immune responses, that protected against lethal infection using EBOV GP-pseudotyped recombinant vesicular stomatitis virus (rVSV-EBOV) in interferon-deficient (Ifnar-/-) mice as surrogate challenge model. Concomitantly induced yellow fever virus (YFV)-specific immunity protected Ifnar-/- mice against intracranial YFV challenge. YF-EBO could thus help to simultaneously combat both EBOV and YFV epidemics. Finally, we demonstrate how to target other highly pathogenic filoviruses such as SUDV at the root of the 2022 outbreak in Uganda.
    DOI:  https://doi.org/10.1038/s41541-023-00699-7
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