An overview of the immune mechanisms of viral myocarditis

Lasrado, Ninaad; Reddy, Jay

doi:10.1002/rmv.2131

Cited by 89 publications

(73 citation statements)

References 174 publications

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“…Myocarditis can occur in association with a wide spectrum of infectious agents (such as viruses, bacteria, and protozoans), systemic immune-mediated diseases, toxic substances, and drugs (such as immune checkpoint inhibitors) ( 2 , 3 , 12 , 13 ). Viruses have been implicated as the leading trigger of myocarditis, with cardiotropic viruses (such as coxsackievirus B3 [CVB3] and adenoviruses), vasculotropic viruses (such as parvovirus B19), and lymphotropic viruses (such as human herpesvirus 6), which are common agents identified in the myocardium of patients with myocarditis/dilated cardiomyopathy (DCM) ( 14 – 16 ). However, the etiologic role of the viruses detected in myocarditis patients is not evident ( 17 ).…”

Section: Triggers Of Myocarditismentioning

confidence: 99%

“…The pathogenesis of CVB3-induced myocarditis involves both viral cytotoxicity and subsequent host immune responses ( 2 ). Initially, CVB3 enters cardiomyocytes by binding to the coxsackievirus-adenovirus receptor, and causes direct cytotoxicity to the myocardium within three to four days post-infection ( 16 ). During the early stage of CVB3 infection, innate immune cells are activated through pattern recognition receptors, such as toll-like receptors (TLRs), and produce pro-inflammatory cytokines, such as interferons (IFNs), interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α ( 16 , 20 ).…”

Section: Triggers Of Myocarditismentioning

confidence: 99%

“…Initially, CVB3 enters cardiomyocytes by binding to the coxsackievirus-adenovirus receptor, and causes direct cytotoxicity to the myocardium within three to four days post-infection ( 16 ). During the early stage of CVB3 infection, innate immune cells are activated through pattern recognition receptors, such as toll-like receptors (TLRs), and produce pro-inflammatory cytokines, such as interferons (IFNs), interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α ( 16 , 20 ). Subsequently, antigen-specific responses in adaptive immune cells are induced, eliminating the virus by up to 14 days post-infection ( 16 , 20 ).…”

Section: Triggers Of Myocarditismentioning

confidence: 99%

“…During the early stage of CVB3 infection, innate immune cells are activated through pattern recognition receptors, such as toll-like receptors (TLRs), and produce pro-inflammatory cytokines, such as interferons (IFNs), interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α ( 16 , 20 ). Subsequently, antigen-specific responses in adaptive immune cells are induced, eliminating the virus by up to 14 days post-infection ( 16 , 20 ). However, even after viral clearance, a subset of individuals may develop chronic myocardial inflammation with virus-triggered uncontrolled immune response and the expansion of cardiac-autoreactive T cells, leading to inflammatory cardiomyopathy.…”

Section: Triggers Of Myocarditismentioning

confidence: 99%

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Immunomodulatory Role of Tenascin-C in Myocarditis and Inflammatory Cardiomyopathy

Tajiri

Yonebayashi

et al. 2021

Front. Immunol.

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Accumulating evidence suggests that the breakdown of immune tolerance plays an important role in the development of myocarditis triggered by cardiotropic microbial infections. Genetic deletion of immune checkpoint molecules that are crucial for maintaining self-tolerance causes spontaneous myocarditis in mice, and cancer treatment with immune checkpoint inhibitors can induce myocarditis in humans. These results suggest that the loss of immune tolerance results in myocarditis. The tissue microenvironment influences the local immune dysregulation in autoimmunity. Recently, tenascin-C (TN-C) has been found to play a role as a local regulator of inflammation through various molecular mechanisms. TN-C is a nonstructural extracellular matrix glycoprotein expressed in the heart during early embryonic development, as well as during tissue injury or active tissue remodeling, in a spatiotemporally restricted manner. In a mouse model of autoimmune myocarditis, TN-C was detectable before inflammatory cell infiltration and myocytolysis became histologically evident; it was strongly expressed during active inflammation and disappeared with healing. TN-C activates dendritic cells to generate pathogenic autoreactive T cells and forms an important link between innate and acquired immunity.

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Section: Triggers Of Myocarditismentioning

confidence: 99%

Section: Triggers Of Myocarditismentioning

confidence: 99%

Section: Triggers Of Myocarditismentioning

confidence: 99%

Section: Triggers Of Myocarditismentioning

confidence: 99%

See 2 more Smart Citations

Immunomodulatory Role of Tenascin-C in Myocarditis and Inflammatory Cardiomyopathy

Tajiri

Yonebayashi

et al. 2021

Front. Immunol.

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“…The copyright holder for this preprint (which this version posted May 17, 2021. ; https://doi.org/10.1101/2021.05.16.444367 doi: bioRxiv preprint 4 mice develop chronic disease, making them suitable to study the pathogenic mechanisms that may involve both viral and host factors 7,9,10 . We routinely use A/J mice that are highly susceptible to a human isolate of the Nancy strain of CVB3 9,11 .…”

Section: Introductionmentioning

confidence: 99%

Dissecting the Cellular Landscape and Transcriptome Network in Viral Myocarditis by Single-Cell RNA Sequencing

Lasrado

Borcherding

Arumugam

et al. 2021

Preprint

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Myocarditis induced with Coxsackievirus B3 (CVB3) is commonly employed to study viral pathogenesis in mice. Although infectious virus is cleared after the acute phase, affected animals chronically develop the features of dilated cardiomyopathy, which may involve the mediation of immune and non-immune cells. To dissect this complexity, we performed single-cell RNA sequencing on heart cells obtained from healthy and myocarditic mice, leading us to note that myocarditic mice had significantly higher proportions of myeloid cells, CD4 and CD8 T cells, and fibroblasts, whereas NK cells, ILCs and B cells were low. While the transcriptome profiles of myeloid cells revealed detection of monocytes and macrophages of M2 phenotype with pathways important in immune metabolism and inflammation, T cells consisted of Th17 cells, CTLs, and Treg cells with transcriptome signatures critical for cytotoxic functions. Although fibroblasts detected in myocarditic mice were phenotypically heterogeneous, their transcriptomes played roles in fibrosis and regulation of inflammation and immune responses. Additionally, analysis of intercellular communication networks revealed unique interactions and signaling pathways in the cardiac cellulome, whereas myeloid cells and T cells in myocarditic mice revealed uniquely upregulated transcription factors modulating cardiac remodeling functions. Taken together, our data suggest that M2 cells, T cells, and fibroblasts may cooperatively or independently participate in the pathogenesis of viral myocarditis.

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Identification of the communal pathogenesis and immune landscape between viral myocarditis and dilated cardiomyopathy

Lei,

Cao,

et al. 2023

ESC Heart Failure

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AimsStudies have confirmed that viral myocarditis (VMC) is one of the risk factors for dilated cardiomyopathy (DCM). The molecular mechanisms underlying the progression from VMC to DCM remain unclear and require further investigation.Methods and resultsThe mRNA microarray datasets GSE57338 (DCM) and GSE1145 (VMC) were obtained from the Gene Expression Omnibus database. The candidate key genes were further screened using weighted correlation network analysis (WGCNA), protein–protein interaction and external dataset validation, and the correlation between the candidate key genes and immune cells and the signalling pathways of the candidate key genes were observed by enrichment analysis and immune infiltration analysis. The expression of key genes was validated in the external dataset GSE35182. The crosstalk genes between DCM and VMC were mainly enriched in ‘transcriptional misregulation in cancer’, ‘FoxO signalling pathway’, ‘AGE‐RAGE signalling pathway in diabetic complications’, ‘thyroid hormone signalling pathway’, ‘AMPK signalling pathway’, and other signalling pathways. The immune infiltration analysis indicated that VMC was mainly associated with resting dendritic cells and M0 macrophages, while DCM was mainly associated with monocytes, M0 macrophages, CD8+ T cells, resting CD4 memory T cells, naive CD4+ T cells, and resting mast cells. In DCM‐related dataset GSE57338 and VMC‐related dataset GSE1145, a total of 18 candidate key genes were differentially expressed. BLC6, FOXO1, and UBE2M were identified as the key genes that lead to the progression from VMC to DCM by GSE35182.ConclusionsThree key genes (BLC6, FOXO1, and UBE2M) were identified and provided new insights into the diagnosis and treatment of VMC with DCM.

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An overview of the immune mechanisms of viral myocarditis

Cited by 89 publications

References 174 publications

Immunomodulatory Role of Tenascin-C in Myocarditis and Inflammatory Cardiomyopathy

Immunomodulatory Role of Tenascin-C in Myocarditis and Inflammatory Cardiomyopathy

Dissecting the Cellular Landscape and Transcriptome Network in Viral Myocarditis by Single-Cell RNA Sequencing

Identification of the communal pathogenesis and immune landscape between viral myocarditis and dilated cardiomyopathy

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