Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Heart Failure Reviews
Published in: Heart Failure Reviews 6/2019

01-11-2019 | Myocarditis

Immune cell diversity contributes to the pathogenesis of myocarditis

Authors: Xiumeng Hua, Jiangping Song

Published in: Heart Failure Reviews | Issue 6/2019

Login to get access

Abstract

Myocarditis (MCD) is a type of inflammatory disease in which inflammatory cells infiltrate the myocardium, leading to cardiac dysfunction, myocardial necrosis, and fibrosis. Although it has been reported that MCD is mediated by T cells, the immune system is complex and includes many types of immune cells that interact with one another. Through investigations of the inflammatory responses in MCD including myocardial necrosis, fibrosis, and arrhythmia, we have gained further insight into the pathogenesis of MCD. This article aims to discuss the diversity and the roles of immune cells involved in the pathogenesis of MCD. Moreover, immunotherapy for the treatment of MCD remains controversial, and further investigation is required to identify accurate immunotherapies for special cell types.
Literature
1.
2.
3.
Leone O, Veinot JP, Angelini A, Baandrup UT, Basso C, Berry G, Bruneval P, Burke M, Butany J, Calabrese F, D'Amati G, Edwards WD, Fallon JT, Fishbein MC, Gallagher PJ, Halushka MK, McManus B, Pucci A, Rodriguez ER, Saffitz JE, Sheppard MN, Steenbergen C, Stone JR, Tan C, Thiene G, van der Wal AC, Winters GL (2012) 2011 consensus statement on endomyocardial biopsy from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology. Cardiovasc Pathol 21:245–274PubMedCrossRef
4.
Heymans S, Eriksson U, Lehtonen J, Cooper LJ (2016) The quest for new approaches in myocarditis and inflammatory cardiomyopathy. J Am Coll Cardiol 68:2348–2364PubMedCrossRef
5.
Mahrholdt H, Wagner A, Deluigi CC, Kispert E, Hager S, Meinhardt G, Vogelsberg H, Fritz P, Dippon J, Bock CT, Klingel K, Kandolf R, Sechtem U (2006) Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation 114:1581–1590PubMedCrossRef
6.
7.
8.
9.
Pinto AR, Paolicelli R, Salimova E, Gospocic J, Slonimsky E, Bilbao-Cortes D, Godwin JW, Rosenthal NA (2012) An abundant tissue macrophage population in the adult murine heart with a distinct alternatively-activated macrophage profile. PLoS One 7:e36814PubMedPubMedCentralCrossRef
10.
Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, Libby P, Weissleder R, Pittet MJ (2007) The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 204:3037–3047PubMedPubMedCentralCrossRef
11.
Choi JH, Do Y, Cheong C, Koh H, Boscardin SB, Oh YS, Bozzacco L, Trumpfheller C, Park CG, Steinman RM (2009) Identification of antigen-presenting dendritic cells in mouse aorta and cardiac valves. J Exp Med 206:497–505PubMedPubMedCentralCrossRef
12.
Frangogiannis NG, Lindsey ML, Michael LH, Youker KA, Bressler RB, Mendoza LH, Spengler RN, Smith CW, Entman ML (1998) Resident cardiac mast cells degranulate and release preformed TNF-alpha, initiating the cytokine cascade in experimental canine myocardial ischemia/reperfusion. Circulation 98:699–710PubMedCrossRef
13.
Kolaczkowska E, Kubes P (2013) Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 13:159–175PubMedCrossRef
14.
Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A (2012) Neutrophil function: from mechanisms to disease. Annu Rev Immunol 30:459–489PubMedCrossRef
15.
Shah AD, Denaxas S, Nicholas O, Hingorani AD, Hemingway H (2017) Neutrophil counts and initial presentation of 12 cardiovascular diseases: a CALIBER cohort study. J Am Coll Cardiol 69:1160–1169PubMedPubMedCentralCrossRef
16.
Zouggari Y, Ait-Oufella H, Bonnin P, Simon T, Sage AP, Guerin C, Vilar J, Caligiuri G, Tsiantoulas D, Laurans L, Dumeau E, Kotti S, Bruneval P, Charo IF, Binder CJ, Danchin N, Tedgui A, Tedder TF, Silvestre JS, Mallat Z (2013) B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Nat Med 19:1273–1280PubMedPubMedCentralCrossRef
17.
Saxena A, Dobaczewski M, Rai V, Haque Z, Chen W, Li N, Frangogiannis NG (2014) Regulatory T cells are recruited in the infarcted mouse myocardium and may modulate fibroblast phenotype and function. Am J Physiol Heart Circ Physiol 307:H1233–H1242PubMedPubMedCentralCrossRef
18.
Tan KL, Scott DW, Hong F, Kahl BS, Fisher RI, Bartlett NL, Advani RH, Buckstein R, Rimsza LM, Connors JM, Steidl C, Gordon LI, Horning SJ, Gascoyne RD (2012) Tumor-associated macrophages predict inferior outcomes in classic Hodgkin lymphoma: a correlative study from the E2496 intergroup trial. Blood 120:3280–3287PubMedPubMedCentralCrossRef
19.
Epelman S, Lavine KJ, Beaudin AE, Sojka DK, Carrero JA, Calderon B, Brija T, Gautier EL, Ivanov S, Satpathy AT, Schilling JD, Schwendener R, Sergin I, Razani B, Forsberg EC, Yokoyama WM, Unanue ER, Colonna M, Randolph GJ, Mann DL (2014) Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity 40:91–104PubMedPubMedCentralCrossRef
20.
Jaquenod DGC, Ure AE, Rivadeneyra L, Schattner M, Gomez RM (2015) Macrophages and galectin 3 play critical roles in CVB3-induced murine acute myocarditis and chronic fibrosis. J Mol Cell Cardiol 85:58–70CrossRef
21.
Wang C, Dong C, Xiong S (2017) IL-33 enhances macrophage M2 polarization and protects mice from CVB3-induced viral myocarditis. J Mol Cell Cardiol 103:22–30PubMedCrossRef
22.
23.
Sapienza MR, Fuligni F, Agostinelli C, Tripodo C, Righi S, Laginestra MA, Pileri AJ, Mancini M, Rossi M, Ricci F, Gazzola A, Melle F, Mannu C, Ulbar F, Arpinati M, Paulli M, Maeda T, Gibellini D, Pagano L, Pimpinelli N, Santucci M, Cerroni L, Croce CM, Facchetti F, Piccaluga PP, Pileri SA (2014) Molecular profiling of blastic plasmacytoid dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB pathway inhibition. Leukemia 28:1606–1616PubMedPubMedCentralCrossRef
24.
Eriksson U, Ricci R, Hunziker L, Kurrer MO, Oudit GY, Watts TH, Sonderegger I, Bachmaier K, Kopf M, Penninger JM (2003) Dendritic cell-induced autoimmune heart failure requires cooperation between adaptive and innate immunity. Nat Med 9:1484–1490PubMedCrossRef
25.
Kretzschmar D, Betge S, Windisch A, Pistulli R, Rohm I, Fritzenwanger M, Jung C, Schubert K, Theis B, Petersen I, Drobnik S, Mall G, Figulla HR, Yilmaz A (2012) Recruitment of circulating dendritic cell precursors into the infarcted myocardium and pro-inflammatory response in acute myocardial infarction. Clin Sci (Lond) 123:387–398CrossRef
26.
27.
Parham P, Guethlein LA (2018) Genetics of natural killer cells in human health, disease, and survival. Annu Rev Immunol 36:519–548PubMedCrossRef
28.
Mace EM, Gunesch JT, Dixon A, Orange JS (2016) Human NK cell development requires CD56-mediated motility and formation of the developmental synapse. Nat Commun 7:12171PubMedPubMedCentralCrossRef
29.
Jost S, Altfeld M (2013) Control of human viral infections by natural killer cells. Annu Rev Immunol 31:163–194PubMedCrossRef
30.
Wernersson S, Pejler G (2014) Mast cell secretory granules: armed for battle. Nat Rev Immunol 14:478–494PubMedCrossRef
31.
Higuchi H, Hara M, Yamamoto K, Miyamoto T, Kinoshita M, Yamada T, Uchiyama K, Matsumori A (2008) Mast cells play a critical role in the pathogenesis of viral myocarditis. Circulation 118:363–372PubMedCrossRef
32.
Meng X, Yang J, Dong M, Zhang K, Tu E, Gao Q, Chen W, Zhang C, Zhang Y (2016) Regulatory T cells in cardiovascular diseases. Nat Rev Cardiol 13:167–179PubMedCrossRef
33.
Song J, Chen X, Cheng L, Rao M, Chen K, Zhang N, Meng J, Li M, Liu ZQ, Yang PC (2018) Vitamin D receptor restricts Th2-biased inflammation in the heart. Cardiovasc Res 114:870–879PubMedCrossRef
34.
Nindl V, Maier R, Ratering D, De Giuli R, Zust R, Thiel V, Scandella E, Di Padova F, Kopf M, Rudin M, Rulicke T, Ludewig B (2012) Cooperation of Th1 and Th17 cells determines transition from autoimmune myocarditis to dilated cardiomyopathy. Eur J Immunol 42:2311–2321PubMedCrossRef
35.
36.
Eriksson U, Kurrer MO, Sebald W, Brombacher F, Kopf M (2001) Dual role of the IL-12/IFN-gamma axis in the development of autoimmune myocarditis: induction by IL-12 and protection by IFN-gamma. J Immunol 167:5464–5469PubMedCrossRef
37.
Eriksson U, Kurrer MO, Bingisser R, Eugster HP, Saremaslani P, Follath F, Marsch S, Widmer U (2001) Lethal autoimmune myocarditis in interferon- γ receptor − deficient mice : enhanced disease severity by impaired inducible nitric oxide synthase induction. Circulation 103:18–21PubMedCrossRef
38.
Ono M, Shimizu J, Miyachi Y, Sakaguchi S (2006) Control of autoimmune myocarditis and multiorgan inflammation by glucocorticoid-induced TNF receptor family-related protein (high), Foxp3-expressing CD25+ and CD25- regulatory T cells. J Immunol 176:4748–4756PubMedCrossRef
39.
Golstein P, Griffiths GM (2018) An early history of T cell-mediated cytotoxicity. Nat Rev Immunol 18:527–535PubMedCrossRef
40.
Yu Y, Ma X, Gong R, Zhu J, Wei L, Yao J (2018) Recent advances in CD8(+) regulatory T cell research. Oncol Lett 15:8187–8194PubMedPubMedCentral
41.
Massilamany C, Gangaplara A, Basavalingappa RH, Rajasekaran RA, Khalilzad-Sharghi V, Han Z, Othman S, Steffen D, Reddy J (2016) Localization of CD8 T cell epitope within cardiac myosin heavy chain-alpha334-352 that induces autoimmune myocarditis in a/J mice. Int J Cardiol 202:311–321PubMedCrossRef
42.
Matsumoto Y, Park IK, Kohyama K (2007) B-cell epitope spreading is a critical step for the switch from C-protein-induced myocarditis to dilated cardiomyopathy. Am J Pathol 170:43–51PubMedPubMedCentralCrossRef
43.
Schulz C, Gomez PE, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SE, Pollard JW, Frampton J, Liu KJ, Geissmann F (2012) A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336:86–90CrossRefPubMed
44.
Molawi K, Wolf Y, Kandalla PK, Favret J, Hagemeyer N, Frenzel K, Pinto AR, Klapproth K, Henri S, Malissen B, Rodewald HR, Rosenthal NA, Bajenoff M, Prinz M, Jung S, Sieweke MH (2014) Progressive replacement of embryo-derived cardiac macrophages with age. J Exp Med 211:2151–2158PubMedPubMedCentralCrossRef
45.
van Amerongen MJ, Harmsen MC, van Rooijen N, Petersen AH, van Luyn MJ (2007) Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice. Am J Pathol 170:818–829PubMedPubMedCentralCrossRef
46.
Li K, Xu W, Guo Q, Jiang Z, Wang P, Yue Y, Xiong S (2009) Differential macrophage polarization in male and female BALB/c mice infected with coxsackievirus B3 defines susceptibility to viral myocarditis. Circ Res 105:353–364PubMedCrossRef
47.
Hulsmans M, Clauss S, Xiao L, Aguirre AD, King KR, Hanley A, Hucker WJ, Wulfers EM, Seemann G, Courties G, Iwamoto Y, Sun Y, Savol AJ, Sager HB, Lavine KJ, Fishbein GA, Capen DE, Da SN, Miquerol L, Wakimoto H, Seidman CE, Seidman JG, Sadreyev RI, Naxerova K, Mitchell RN, Brown D, Libby P, Weissleder R, Swirski FK, Kohl P, Vinegoni C, Milan DJ, Ellinor PT, Nahrendorf M (2017) Macrophages facilitate electrical conduction in the heart. Cell 169:510–522.e20PubMedPubMedCentralCrossRef
48.
Uemura A, Morimoto S, Hiramitsu S, Hishida H (2001) Endomyocardial biopsy findings in 50 patients with idiopathic atrioventricular block: presence of myocarditis. Jpn Heart J 42:691–700PubMedCrossRef
49.
Kania G, Siegert S, Behnke S, Prados-Rosales R, Casadevall A, Luscher TF, Luther SA, Kopf M, Eriksson U, Blyszczuk P (2013) Innate signaling promotes formation of regulatory nitric oxide-producing dendritic cells limiting T-cell expansion in experimental autoimmune myocarditis. Circulation 127:2285–2294PubMedCrossRef
50.
Griffin GK, Lichtman AH (2013) Two sides to every proinflammatory coin: new insights into the role of dendritic cells in the regulation of T-cell driven autoimmune myocarditis. Circulation 127:2257–2260PubMedPubMedCentralCrossRef
51.
Fairweather D, Kaya Z, Shellam GR, Lawson CM, Rose NR (2001) From infection to autoimmunity. J Autoimmun 16(3):175–186PubMedCrossRef
52.
Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S (2008) Functions of natural killer cells. Nat Immunol 9:503–510PubMedCrossRef
53.
54.
St JA, Abraham SN (2013) Innate immunity and its regulation by mast cells. J Immunol 190:4458–4463CrossRef
55.
Liu ZQ, Song JP, Liu X, Jiang J, Chen X, Yang L, Hu T, Zheng PY, Liu ZG, Yang PC (2014) Mast cell-derived serine proteinase regulates T helper 2 polarization. Sci Rep 4:4649PubMedPubMedCentralCrossRef
56.
Gieseck RR, Wilson MS, Wynn TA (2017) Type 2 immunity in tissue repair and fibrosis. Nat Rev Immunol 18:62–76PubMedCrossRef
57.
58.
Blyszczuk P, Muller-Edenborn B, Valenta T, Osto E, Stellato M, Behnke S, Glatz K, Basler K, Luscher TF, Distler O, Eriksson U, Kania G (2017) Transforming growth factor-beta-dependent Wnt secretion controls myofibroblast formation and myocardial fibrosis progression in experimental autoimmune myocarditis. Eur Heart J 38:1413–1425PubMed
59.
Opavsky MA, Penninger J, Aitken K, Wen WH, Dawood F, Mak T, Liu P (1999) Susceptibility to myocarditis is dependent on the response of alphabeta T lymphocytes to coxsackieviral infection. Circ Res 85:551–558PubMedCrossRef
60.
Smith SC, Allen PM (1991) Myosin-induced acute myocarditis is a T cell-mediated disease. J Immunol 147:2141–2147PubMed
61.
Penninger JM, Pummerer C, Liu P, Neu N, Bachmaier K (1997) Cellular and molecular mechanisms of murine autoimmune myocarditis. APMIS 105:1–13PubMedCrossRef
62.
Chen P, Baldeviano GC, Ligons DL, Talor MV, Barin JG, Rose NR, Cihakova D (2012) Susceptibility to autoimmune myocarditis is associated with intrinsic differences in CD4(+) T cells. Clin Exp Immunol 169:79–88PubMedPubMedCentralCrossRef
63.
Bonelli M, Shih HY, Hirahara K, Singelton K, Laurence A, Poholek A, Hand T, Mikami Y, Vahedi G, Kanno Y, O'Shea JJ (2014) Helper T cell plasticity: impact of extrinsic and intrinsic signals on transcriptomes and epigenomes. Curr Top Microbiol Immunol 381:279–326PubMedPubMedCentral
64.
Borst J, Ahrends T, Babala N, Melief C, Kastenmuller W (2018) CD4(+) T cell help in cancer immunology and immunotherapy. Nat Rev Immunol 18:635–647PubMedCrossRef
65.
66.
Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander MR, Bloomer TL, Becker JR, Slosky DA, Phillips EJ, Pilkinton MA, Craig-Owens L, Kola N, Plautz G, Reshef DS, Deutsch JS, Deering RP, Olenchock BA, Lichtman AH, Roden DM, Seidman CE, Koralnik IJ, Seidman JG, Hoffman RD, Taube JM, Diaz LJ, Anders RA, Sosman JA, Moslehi JJ (2016) Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med 375:1749–1755PubMedPubMedCentralCrossRef
67.
Chaigne B, Mouthon L (2017) Mechanisms of action of intravenous immunoglobulin. Transfus Apher Sci 56(1):45–49PubMedCrossRef
68.
Orange J, Hossny E, Weiler C, Ballow M, Berger M, Bonilla F, Buckley R, Chinen J, Elgamal Y, Mazer B (2006) Use of intravenous immunoglobulin in human disease: a review of evidence by members of the primary immunodeficiency Committee of the American Academy of allergy, asthma and immunology. J Allergy Clin Immunol 117(4):S525–S553PubMedCrossRef
69.
Neubert K, Meister S, Moser K, Weisel F, Maseda D, Amann K, Wiethe C, Winkler TH, Kalden JR, Manz RA, Voll RE (2008) The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis. Nat Med 14(7):748–755PubMedCrossRef
70.
Nikolaev VO, Boivin V, Störk S, Angermann CE, Ertl G, Lohse MJ, Jahns R (2007) A novel fluorescence method for the rapid detection of functional Î21-adrenergic receptor autoantibodies in heart failure. J Am Coll Cardiol 50(5):423–431PubMedCrossRef
71.
Mobini R, Staudt A, Felix SB, Baumann G, Wallukat G, Deinum J, Svensson H, Hjalmarson Å, Michael F (2003) Hemodynamic improvement and removal of autoantibodies against β -adrenergic receptor by immunoadsorption therapy in dilated cardiomyopathy. J Autoimmun 20(4):345–350PubMedCrossRef
72.
Trimpert C, Herda LR, Eckerle LG, Pohle S, Müller C, Landsberger M, Felix SB, Staudt A (2010) Immunoadsorption in dilated cardiomyopathy: long-term reduction of cardiodepressant antibodies. Eur J Clin Investig 40(8):685–691CrossRef
73.
Felix SB, Staudt A, Landsberger M, Grosse Y, Stangl V, Spielhagen T, Wallukat G, Wernecke KD, Baumann G, Stangl K (2002) Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption. J Am Coll Cardiol 39(4):646–652PubMedCrossRef
74.
75.
Schmeits PCJ, Schaap MM, Luijten M, van Someren E, Boorsma A, van Loveren H, Peijnenburg AACM, Hendriksen PJM (2015) Detection of the mechanism of immunotoxicity of cyclosporine a in murine in vitro and in vivo models. Arch Toxicol 89(12):2325–2337PubMedCrossRef
76.
Winter MP, Sulzgruber P, Koller L, Bartko P, Goliasch G, Niessner A (2018) Immunomodulatory treatment for lymphocytic myocarditis-a systematic review and meta-analysis. Heart Fail Rev 23:573–581PubMedPubMedCentralCrossRef
77.
Matsumoto Y, Jee Y, Sugisaki M (2000) Successful TCR-based immunotherapy for autoimmune myocarditis with DNA vaccines after rapid identification of pathogenic TCR. J Immunol 164:2248–2254PubMedCrossRef
78.
Tarrio ML, Grabie N, Bu DX, Sharpe AH, Lichtman AH (2012) PD-1 protects against inflammation and myocyte damage in T cell-mediated myocarditis. J Immunol 188:4876–4884PubMedCrossRef
Metadata
Title
Immune cell diversity contributes to the pathogenesis of myocarditis
Authors
Xiumeng Hua
Jiangping Song
Publication date
01-11-2019
Publisher
Springer US
Keyword
Myocarditis
Published in
Heart Failure Reviews / Issue 6/2019
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI
https://doi.org/10.1007/s10741-019-09799-w

Other articles of this Issue 6/2019

Heart Failure Reviews 6/2019 Go to the issue

ReviewPaper

Sudden death in heart failure with preserved ejection fraction and beyond: an elusive target

ReviewPaper

Biomarkers in heart failure: the past, current and future

ReviewPaper

Patients with high-dose diuretics should get ultrafiltration in the management of decompensated heart failure: a meta-analysis

ReviewPaper

Advances in research on treatment of heart failure with nitrosyl hydrogen

ReviewPaper

Cardio-oncology, the myth of Sisyphus, and cardiovascular disease in breast cancer survivors

ReviewPaper

Takotsubo syndrome: an overview of pathophysiology, diagnosis and treatment with emphasis on cancer patients

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits