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. 2021 May 5;8:675339. doi: 10.3389/fcvm.2021.675339

Table 1.

Immunopathological changes in small animals and rodents investigated as experimental model for post streptococcal complications.

Antigens (route of injection) Histological changes Antibody response T-cell and cytokine response Tissue cross reactivity References
Cardiac pathology
Mice Cell wall fragments of GAS (i.p.) Myocarditis, valvulitis MNCs, anitschkow cell, PMNCs Anti-GAS IgG collagen IV reactive IgG N/A Basement membrane collagen (20, 43)
Recombinant proteins/peptides of GAS (f.p., s.c.) Myocarditis, valvulitis Anti-GAS IgG CD4+ (M) Myosin (77)
Lewis rats Whole GAS and/or SDSE (f.p., s.c.) Myocarditis, valvulitis monocyte, fibroblast, aschoff like cell lymphocyte, macrophages Anti-streptococcal IgG Anti-myocardial IgG, antistreptolysin O CD3+ (M), CD68+ (M), IFN-γ 🠙 (B), IL-17A 🠙 (B), IL-4 🠙 (B) Myocardial protein, valvular protein, cardiac myosin, collagen (31, 32, 35, 36)
Recombinant proteins/peptides of GAS and/or SDSE (f.p., s.c.) Myocarditis, valvulitis T-cell, MNCs, PMNCs, anitschkow cell Anti-myosin IgG Anti- collagen IgG CD3+ (M), CD4+ (M), CD8+ (M), CD68+ (M), IFN-γ 🠙, IL-17A 🠙, IL-4 🠙 Myosin, valvular protein, collagen (26, 27, 30, 3436)
Serum from GAS exposed rats (s.c.) Myocarditis, valvulitis T-cell, MNCs, PMNCs, anitschkow cell Anti-myosin IgG CD4+ (M) Myosin, valvular protein, collagen (36)
Guinea pig Whole GAS (s.c., f.p., i.m., i.v.) Myocarditis, valvulitis B-cell, macrophages, MNCs, fibroblast, cytotoxic lymphocytes Anti-streptococcal IgG N/A Cardiac myofibre, sarcolemma (23, 25)
Cell wall fragments of GAS (s.c., f.p., i.m.) Myocarditis, valvulitis B-cell, macrophages, fibroblast, cytotoxic lymphocytes Anti-streptococcal IgG N/A Cardiac myofibre, sarcolemma (25)
Rabbit Whole GAS (s.c., f.p., i.m., i.v., i.d., i.p.) Myocarditis, valvulitis lymphocyte, MNCs, leukocyte, aschoff bodies, fibroblast, fibrin, collagen N/A N/A Skeletal muscle (2325)
Cell wall fragments of GAS (s.c., f.p., i.m., i.v., i.d.) Myofibrosis with degeneration of sarcoplasm, lymphocyte, macrophages, granulocyte Anti-myosin IgG, Anti-sarcolemmal Ig T-cell, IL-6 🠙, C3 (CV) Sarcolemmal membrane protein, myosin (25, 28, 29, 78)
Neurobehavioral changes
Mice Whole GAS (s.c., i.n) Antibody deposition deep cerebellar nuclei globus pallidum, thalamus, periventricular areas Anti-GAS IgG CD4+, CD68+Iba1+ Th1 🠙, Th17 🠙, IL-17A 🠙, IFN-γ 🠙(B) N/A (57, 61, 62, 67)
Serum from GAS exposed mice (s.c.) Antibody deposition hippocampus periventricular area Anti-GAS IgG1 IL-4 🠙 (B) N/A (58)
Lewis rats Whole GAS (s.c.) Antibody deposition striatum, thalamus, and frontal cortex Anti-GAS IgG Anti-dopamine IgG N/A Dopamine D1R and D2L receptors (59)
Serum from GAS exposed rats (s.c.) Antibody deposition striatum Anti-GAS IgG N/A Dopamine D1R and D2L, serotonin transporter (60)

f.p., foot pad; i.v., intra venous; i.m., intra muscular; i.d., intra dermal; s.c., sub cutaneous; i.p., intra peritoneal; CV, Cardiac Valve; C, Complement; B, Blood; GAS, Group A streptococci; IFN, Interferon; IgG, Immunoglobulin G; IL, Interleukin; MNC, Mononuclear Cell; M, Myocardium; SDSE, Streptococcus dysgalactiae subspecies equisimilis; PMNC, Polymorphonuclear cells; Th, helper T-cell; TNF, Tumor necrosis factor; 🠙, Elevated; N/A, Not Assessed.