Role of natural killer cells in experimental murine myocarditis

Gauntt, Charles J.; Godeny, Elmer K.; Lutton, C. William; Fernandes, Gabriel

doi:10.1007/bf00197084

Cited by 17 publications

(6 citation statements)

References 31 publications

(35 reference statements)

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“…Clinically, deficits in NK cell levels may contribute to low grade cardiac inflammation [55–57]. In this review, we examine the ability of NK cells to modulate the inflammatory response accompanying several heart diseases and discuss how these cells may provide a target for future biological therapies.…”

Section: Heart Disease Accompanied By Inflammationmentioning

confidence: 99%

Natural killer cells in inflammatory heart disease

Ong

Rose

Čiháková

2017

Clinical Immunology

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Despite of a multitude of excellent studies, the regulatory role of natural killer (NK) cells in the pathogenesis of inflammatory cardiac disease is greatly underappreciated. Clinical abnormalities in the numbers and functions of NK cells are observed in myocarditis and inflammatory dilated cardiomyopathy (DCMi) as well as in cardiac transplant rejection [1–6]. Because treatment of these disorders remains largely symptomatic in nature, patients have little options for targeted therapies [7, 8]. However, blockade of NK cells and their receptors can protect against inflammation and damage in animal models of cardiac injury and inflammation. In these models, NK cells suppress the maturation and trafficking of inflammatory cells, alter the local cytokine and chemokine environments, and induce apoptosis in nearby resident and hematopoietic cells [1, 9, 10]. This review will dissect each protective mechanism employed by NK cells and explore how their properties might be exploited for their therapeutic potential.

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Section: Heart Disease Accompanied By Inflammationmentioning

confidence: 99%

Natural killer cells in inflammatory heart disease

Ong

Rose

Čiháková

2017

Clinical Immunology

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“…NK-T cells, however, favor generation of Treg cells and dampen the inflammatory response triggered by γδ T cells. γδ T cells also can induce cardiac damage by killing the virus-infected CD1d-expressing cardiomyocytes by Fas/Fas-L pathway [72-74], while NK cells are protective in CVB3-induced myocarditis: mice depleted of NK cells showed increased viral titers and exacerbated myocarditis [75, 76]. Recent studies indicate that CVB3 infection can lead to degranulation of mast cells within 6 hours postinfection and to production of proinflammatory cytokines (IL-1, IL-6, IL-8, TNF-α, granulocyte macrophage-colony stimulating factor and other molecules (histamine, heparin, and proteases).…”

Section: Pathogenesis Of Cvb3 Infectionmentioning

confidence: 99%

Intricacies of cardiac damage in coxsackievirus B3 infection: Implications for therapy

Massilamany

Gangaplara

Reddy

2014

International Journal of Cardiology

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Heart disease is the leading cause of death in humans, and myocarditis is one predominant cause of heart failure in young adults. Patients affected with myocarditis can develop dilated cardiomyopathy (DCM), a common reason for heart transplantation, which to date is the only viable option for combatting DCM. Myocarditis/DCM patients show antibodies to coxsackievirus B (CVB)3 and cardiac antigens, suggesting a role for CVB-mediated autoimmunity in the disease pathogenesis; however, a direct causal link remains to be determined clinically. Experimentally, myocarditis can be induced in susceptible strains of mice using the human isolates of CVB3, and the disease pathogenesis of postinfectious myocarditis resembles that of human disease, making the observations made in animals relevant to humans. In this review, we discuss the complex nature of CVB3-induced myocarditis as it relates to the damage caused by both the virus and the host's response to infection. Based on recent data we obtained in the mouse model of CVB3 infection, we provide evidence to suggest that CVB3 infection accompanies the generation of cardiac myosin-specific CD4 T cells that can transfer the disease to naïve recipients. The therapeutic implications of these observations are also discussed.

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“…9 Conversely, inhibition of natural killer cells in virus-infected mice or CVB3 infection of B-cell-knockout (KO) animals exacerbates disease. 10,11 Matrix metalloproteinases (MMPs) are important immunomodulators through their matrix-degrading functions, affecting cytokine processing and cell migration. 12,13 MMP-8 and MMP-9 regulate both innate and adaptive immunities.…”

Section: Clinical Perspective P 1582mentioning

confidence: 99%

Ablation of Matrix Metalloproteinase-9 Increases Severity of Viral Myocarditis in Mice

et al. 2008

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Background-Coxsackievirus B3 (CVB3) causes human myocarditis, which can result in cardiac damage, maladaptive remodeling, and heart failure. Matrix metalloproteinases (MMP)-8 and -9 have been identified in virus-infected myocardium, but their particular roles and underlying mechanisms of effect are unknown. For the first time, we examine the severity of CVB3-induced myocarditis in MMP-8 -and MMP-9 -deficient mice. Methods and Results-CVB3-infected MMP-8 and MMP-9 knockout (KO) mice and corresponding wild-type (WT) mice were euthanized and harvested at 9 days after infection. Expression of MMP-2, -8, -12, and -13 and tissue inhibitors of MMPs was assessed by zymography or immunoblotting on harvested hearts, and in situ hybridization was performed to detect active infection. Infected MMP-9 KO mice had greater myocardial injury and foci of infection than WT mice despite similar pancreatic infection. Increased fibrosis (10.6Ϯ2.7% versus 7.1Ϯ2.6%, Pϭ0.04), viral titer, as well as decreased cardiac output, were evident in MMP-9 KO compared with WT mice as assessed by picrosirius red staining, plaque assay, and echocardiography, respectively. Immune infiltration was also greatly increased in MMP-9 KO compared with WT mice (15.2Ϯ12.6% versus 2.0Ϯ3.0%, PϽ0.002). Myocardial interferon-␤1, interferon-␥, interleukin-6, interleukin-10, and macrophage inflammatory protein-1␣ expression was elevated in MMP-9 KO mice as measured by quantitative real-time polymerase chain reaction and ELISA. In contrast, MMP-8 KO mice had the same degree of cardiac injury, fibrosis, and viral infection as their WT counterparts. Conclusions-During acute CVB3 infection, MMP-9 appears necessary to halt virus propagation in the heart, promote proper immune infiltration and remodeling, and preserve cardiac output.

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Role of natural killer cells in experimental murine myocarditis

Cited by 17 publications

References 31 publications

Natural killer cells in inflammatory heart disease

Natural killer cells in inflammatory heart disease

Intricacies of cardiac damage in coxsackievirus B3 infection: Implications for therapy

Ablation of Matrix Metalloproteinase-9 Increases Severity of Viral Myocarditis in Mice

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