bims-traimu 2022-12-18 papers

bims-traimu

Biomed News

on Trained immunity

Issue of 2022–12–18
eight papers selected by
Yantong Wan, Southern Medical University

Involvement of trained immunity during autoimmune responses.
Cross-Generational Impact of Innate Immune Memory Following Pregnancy Complications.
Candida albicans V132 induces trained immunity and enhances the responses triggered by the polybacterial vaccine MV140 for genitourinary tract infections.
The spectrum of tuberculosis described as differential DNA methylation patterns in alveolar macrophages and alveolar T cells.
The Innate Immune System in Cardiovascular Diseases and Its Role in Doxorubicin-Induced Cardiotoxicity.
Induction of Innate Memory in Human Monocytes Exposed to Mixtures of Bacterial Agents and Nanoparticles.
Endogenous drivers of altered immune cell metabolism.
Early-life β-glucan exposure enhances disease resilience of broiler chickens to a natural Clostridium perfringens infection.

J Autoimmun. 2022 Dec 14. pii: S0896-8411(22)00164-0. [Epub ahead of print] 102956

Involvement of trained immunity during autoimmune responses.

Valentina P Mora, Ricardo A Loaiza, Jorge A Soto, Karen Bohmwald, Alexis M Kalergis.

  Recently, it has been described that innate immune cells such as monocytes, macrophages, and natural killer cells can develop a non-specific immune response induced by different stimuli, including lipopolysaccharides, Mycobacterium bovis Bacillus Calmette-Guérin, and oxidized low-density lipoprotein. This non-specific immune response has been named "trained immunity," whose mechanism is essential for host defense and vaccine response, promoting better infection control. However, limited information about trained immunity in other non-infectious diseases, such as autoimmune illness, has been reported. The complexity of autoimmune pathology arises from dysfunctions in the innate and adaptive immune systems, triggering different clinical outcomes depending on the disease. Nevertheless, T and B cell function dysregulation is the most common characteristic associated with autoimmunity by promoting the escape from central and peripheral tolerance. Despite the importance of adaptative immunity to autoimmune diseases, the innate immune system also plays a prominent and understudied role in these pathologies. Accordingly, epigenetic and metabolic changes associated with innate immune cells that undergo a trained process are possible new therapeutic targets for autoimmune diseases. Even so, trained immunity can be beneficial or harmful in autoimmune diseases depending on several factors associated with the stimuli. Here, we reviewed the role of trained immunity over the innate immune system and the possible role of these changes in common autoimmune diseases, including Systemic Lupus Erythematosus, Rheumatoid Arthritis, Multiple Sclerosis, and Type 1 Diabetes.

Keywords:  Autoimmune diseases; Autoimmunity; Cellular reprogramming; Innate immune system; Trained immunity

DOI:  https://doi.org/10.1016/j.jaut.2022.102956
Cells. 2022 Dec 06. pii: 3935. [Epub ahead of print]11(23):

Cross-Generational Impact of Innate Immune Memory Following Pregnancy Complications.

Nakeisha A Lodge-Tulloch, Alexa J Toews, Aline Atallah, Tiziana Cotechini, Sylvie Girard, Charles H Graham.

  Pregnancy complications can have long-term negative effects on the health of the affected mothers and their children. In this review, we highlight the underlying inflammatory etiologies of common pregnancy complications and discuss how aberrant inflammation may lead to the acquisition of innate immune memory. The latter can be described as a functional epigenetic reprogramming of innate immune cells following an initial exposure to an inflammatory stimulus, ultimately resulting in an altered response following re-exposure to a similar inflammatory stimulus. We propose that aberrant maternal inflammation associated with complications of pregnancy increases the cross-generational risk of developing noncommunicable diseases (i.e., pregnancy complications, cardiovascular disease, and metabolic disease) through a process mediated by innate immune memory. Elucidating a role for innate immune memory in the cross-generational health consequences of pregnancy complications may lead to the development of novel strategies aimed at reducing the long-term risk of disease.

Keywords:  DOHaD; cross-generational; inflammation; innate immune memory; pregnancy complications; trained immunity

DOI:  https://doi.org/10.3390/cells11233935
Front Immunol. 2022 ;13 1066383

Candida albicans V132 induces trained immunity and enhances the responses triggered by the polybacterial vaccine MV140 for genitourinary tract infections.

Leticia Martín-Cruz, Alba Angelina, Ilayda Baydemir, Özlem Bulut, José Luis Subiza, Mihai G Netea, Jorge Domínguez-Andrés, Oscar Palomares.

   Introduction: Recurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems all over the world. Antibiotics and antifungals are widely used for such infectious diseases, which is linked with microbial resistances and microbiota deleterious effects. The development of novel approaches for genitourinary tract infections (GUTIs) such as trained immunity-based vaccines (TIbV) is therefore highly required. MV140 is a sublingual whole-cell heat-inactivated polybacterial preparation with demonstrated clinical efficacy for RUTIs. The sublingual heat-inactivated Candida albicans vaccine V132 has been developed for RVVCs. We previously showed that the combination of MV140 and V132 promotes potent Th1/Th17 and regulatory T-cell responses against antigens contained in the formulation and unrelated antigens. The specific contribution of each preparation to such effects and the underlying molecular mechanisms remain incompletely understood.
Methods: PBMC and monocytes were isolated from healthy donors and in vitro stimulated with V132, MV140 or MV140/V132. After 6 days of resting, cells were reestimulated with LPS and MV140. Analysis of cytokine production by ELISA, Seahorse assays for functional metabolic experiments and chromatin immunoprecipitation assays were performed. BALB/c mice were intraperitoneally and sublingually immunized with V132.
Results: We uncover that V132 induces trained immunity in human PBMCs and purified monocytes, significantly increasing the responses triggered by subsequent stimulation with MV140. Mechanistically, V132 drives metabolic rewiring towards increased glycolysis and oxidative phosphorylation and induces epigenetic reprogramming that enhances the transcription of the pro-inflammatory genes IL6 and TNFA. Splenocytes and peritoneal cells from V132-immunize mice show increased responses upon in vitro stimulation with MV140. Remarkably, splenocytes from sublingually V132-immunized and MV140 in vivo treatment mice show stronger Th17 responses than mice exposed to excipients upon in vitro stimulation with MV140.
Conclusion: Overall, we provide novel mechanistic insights into how V132-induced trained immunity enhances both innate and adaptive immune responses triggered by MV140, which might open the door for new interventions for GUTIs with important clinical implications.

Keywords:  candida albicans V132; genito urinary infections; metabolic and epigenetic reprogramming; polybacterial preparation MV140; trained immunity

DOI:  https://doi.org/10.3389/fimmu.2022.1066383
Clin Epigenetics. 2022 Dec 17. 14(1): 175

The spectrum of tuberculosis described as differential DNA methylation patterns in alveolar macrophages and alveolar T cells.

Isabelle Pehrson, Shumaila Sayyab, Jyotirmoy Das, Nina Idh, Jakob Paues, Melissa Méndez-Aranda, César Ugarte-Gil, Maria Lerm.

   BACKGROUND: Host innate immune cells have been identified as key players in the early eradication of Mycobacterium tuberculosis and in the maintenance of an anti-mycobacterial immune memory, which we and others have shown are induced through epigenetic reprogramming. Studies on human tuberculosis immunity are dominated by those using peripheral blood as surrogate markers for immunity. We aimed to investigate DNA methylation patterns in immune cells of the lung compartment by obtaining induced sputum from M. tuberculosis- exposed subjects including symptom-free subjects testing positively and negatively for latent tuberculosis as well as patients diagnosed with active tuberculosis. Alveolar macrophages and alveolar T cells were isolated from the collected sputum and DNA methylome analyses performed (Illumina Infinium Human Methylation 450 k).
RESULTS: Multidimensional scaling analysis revealed that DNA methylomes of cells from the tuberculosis-exposed subjects and controls appeared as separate clusters. The numerous genes that were differentially methylated between the groups were functionally connected and overlapped with previous findings of trained immunity and tuberculosis. In addition, analysis of the interferon-gamma release assay (IGRA) status of the subjects demonstrated that the IGRA status was reflected in the DNA methylome by a unique signature.
CONCLUSIONS: This pilot study suggests that M. tuberculosis induces epigenetic reprogramming in immune cells of the lung compartment, reflected as a specific DNA methylation pattern. The DNA methylation signature emerging from the comparison of IGRA-negative and IGRA-positive subjects revealed a spectrum of signature strength with the TB patients grouping together at one end of the spectrum, both in alveolar macrophages and T cells. DNA methylation-based biosignatures could be considered for further development towards a clinically useful tool for determining tuberculosis infection status and the level of tuberculosis exposure.

Keywords:  Biosignature; DNA methylation; Epigenetics; IGRA; Sputum induction; Tuberculosis

DOI:  https://doi.org/10.1186/s13148-022-01390-9
Int J Mol Sci. 2022 Nov 24. pii: 14649. [Epub ahead of print]23(23):

The Innate Immune System in Cardiovascular Diseases and Its Role in Doxorubicin-Induced Cardiotoxicity.

Anchit Bhagat, Pradeep Shrestha, Eugenie S Kleinerman.

  Innate immune cells are the early responders to infection and tissue damage. They play a critical role in the initiation and resolution of inflammation in response to insult as well as tissue repair. Following ischemic or non-ischemic cardiac injury, a strong inflammatory response plays a critical role in the removal of cell debris and tissue remodeling. However, persistent inflammation could be detrimental to the heart. Studies suggest that cardiac inflammation and tissue repair needs to be tightly regulated such that the timely resolution of the inflammation may prevent adverse cardiac damage. This involves the recognition of damage; activation and release of soluble mediators such as cytokines, chemokines, and proteases; and immune cells such as monocytes, macrophages, and neutrophils. This is important in the context of doxorubicin-induced cardiotoxicity as well. Doxorubicin (Dox) is an effective chemotherapy against multiple cancers but at the cost of cardiotoxicity. The innate immune system has emerged as a contributor to exacerbate the disease. In this review, we discuss the current understanding of the role of innate immunity in the pathogenesis of cardiovascular disease and dox-induced cardiotoxicity and provide potential therapeutic targets to alleviate the damage.

Keywords:  anthracyclines; cardiovascular disease; doxorubicin; doxorubicin-induced cardiotoxicity; innate immunity; neutrophil elastase; neutrophils

DOI:  https://doi.org/10.3390/ijms232314649
Int J Mol Sci. 2022 Nov 24. pii: 14655. [Epub ahead of print]23(23):

Induction of Innate Memory in Human Monocytes Exposed to Mixtures of Bacterial Agents and Nanoparticles.

Giacomo Della Camera, Tinghao Liu, Wenjie Yang, Yang Li, Victor F Puntes, Sabrina Gioria, Paola Italiani, Diana Boraschi.

  We assessed whether concomitant exposure of human monocytes to bacterial agents and different engineered nanoparticles can affect the induction of protective innate memory, an immune mechanism that affords better resistance to diverse threatening challenges. Monocytes were exposed in vitro to nanoparticles of different chemical nature, shape and size either alone or admixed with LPS, and cell activation was assessed in terms of production of inflammatory (TNFα, IL-6) and anti-inflammatory cytokines (IL-10, IL-1Ra). After return to baseline conditions, cells were re-challenged with LPS and their secondary "memory" response measured. Results show that nanoparticles alone are essentially unable to generate memory, while LPS induced a tolerance memory response (less inflammatory cytokines, equal or increased anti-inflammatory cytokines). LPS-induced tolerance was not significantly affected by the presence of nanoparticles during the memory generation phase, although with substantial donor-to-donor variability. This suggests that, despite the overall lack of significant effects on LPS-induced innate memory, nanoparticles may have donor-specific effects. Thus, future nanosafety assessment and nanotherapeutic strategies will need a personalized approach in order to ensure both the safety and efficacy of nano medical compounds for individual patients.

Keywords:  LPS; bacteria; innate immunity; innate memory; macrophages; monocytes; nanoparticles

DOI:  https://doi.org/10.3390/ijms232314655
Exp Biol Med (Maywood). 2022 Dec 13. 15353702221134093

Endogenous drivers of altered immune cell metabolism.

Lianne C Shanley, Hannah K Fitzgerald, Sinead A O'Rourke, Aisling Dunne.

  Dysregulated metabolism has long been recognized as a feature of many metabolic disorders. However, recent studies demonstrating that metabolic reprogramming occurs in immune cells have led to a growing interest in the relationship between metabolic rewiring and immune-mediated disease pathogeneses. It is clear now that immune cell subsets engage in different metabolic pathways depending on their activation and/or maturation state. As a result, it may be possible to modulate metabolic reprogramming for clinical benefit. In this review, we provide an overview of immune cell metabolism with focus on endogenous drivers of metabolic reprogramming given their link to a number of immune-mediated disorders.

Keywords:  Immunometabolism; cellular respiration; damage or disease-associated molecular patterns; metabolic reprogramming

DOI:  https://doi.org/10.1177/15353702221134093
Dev Comp Immunol. 2022 Dec 07. pii: S0145-305X(22)00275-0. [Epub ahead of print]140 104613

Early-life β-glucan exposure enhances disease resilience of broiler chickens to a natural Clostridium perfringens infection.

Wanwei He, Mohammad Kamely, Jeremy Wakaruk, Emanuele C Goes, Douglas R Korver, Daniel R Barreda.

  Necrotic enteritis (NE) is an economically important disease in poultry. Colonization by the opportunistic pathogen C. perfringens occurs early after hatch and induces host immune tolerance, which allows it to persist as part of the bird's commensal microflora. β-glucan, a yeast cell wall component, is well characterized for its immunomodulatory capacity, and is a strong driver of innate immune memory. In this study, we assessed the effectiveness of β-glucan to reduce severity of NE, when co-administered with heat-killed C. perfringens via intra-abdominal route at day 1 of age. We found that this early-life exposure in the presence of β-glucan did not reduce intestinal C. perfringens loads or lesion severity during a subsequent NE outbreak. However, it improved ileal morphology, prevented liver and spleen weight decline, and preserved feed efficiency in challenged birds. Molecular analyses revealed metabolic changes consistent with innate immune memory. Together, our results suggest that β-glucan can reduce the negative impacts of NE by influencing the context in which C. perfringens is first encountered.

Keywords:  Clostridium perfringens; Innate immunity; Natural avian infection; Necrotic enteritis

DOI:  https://doi.org/10.1016/j.dci.2022.104613