Cyclin and Caveolin Expression in an Acute Model of Murine Chagasic Myocarditis

Nagajyothi, Fnu; Desruisseaux, Mahalia S.; Bouzahzah, Boumediene; Weiss, Louis M.; Andrade, Daniele; Factor, Stephen M.; Scherer, Philipp E.; Albanese, Chris; Lisanti, Michael P.; Tanowitz, Herbert B.

doi:10.4161/cc.5.1.2284

Cited by 26 publications

(9 citation statements)

References 39 publications

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“…Our results are consistent with older reports of arteritis in skeletal muscle, skin, nerve, heart, and other tissues associated with adventitial infiltration by lymphocytes and macrophages in chronically T. cruzi-infected mice (3)(4)(5)(6)(7)(8)(9)(10)19), as well as skeletal muscle vasculitis in T. cruzi-infected humans (20). We extend these earlier studies by providing the first detailed description of the cellular and humoral immune responses in the lesions.…”

Section: Discussionsupporting

confidence: 92%

Trypanosoma cruzi Causes Paralyzing Systemic Necrotizing Vasculitis Driven by Pathogen-Specific Type I Immunity in Mice

et al. 2016

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dInfectious agents are often considered potential triggers of chronic inflammatory disease, including autoimmunity; however, direct evidence is usually lacking. Here we show that following control of acute infection of mice with the myotropic Colombiana strain of Trypanosoma cruzi, parasites persisted in tissue at low levels associated with development of systemic necrotizing vasculitis. Lesions occurred in many but not all organs and tissues, with skeletal muscle arteries being the most severely affected, and were associated with myositis, atrophy, paresis/paralysis, and death. Histopathology showed fibrinoid vascular necrosis, rare amastigote nests within skeletal muscle myocytes, and massive leukocyte infiltrates composed mainly of inflammatory monocytes, F4/80 ؉ macrophages, and T. cruzi tetramer-specific CD8 ؉ T lymphocytes capable of producing gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣) but not interleukin-17 (IL-17). T. cruzi-specific IgG was detected in sera from infected mice, but antibody deposits and neutrophilic inflammation were not features of the lesions. Thus, T. cruzi infection of mice may be a specific infectious trigger of paralyzing systemic necrotizing vasculitis most severely affecting skeletal muscle, driven by pathogen-specific type I immune responses. Vasculitis is a general term for a spectrum of diseases involving leukocyte infiltration of the blood vessel wall. Many subtypes of vasculitis are recognized based on the types of blood vessels involved and the nature of the underlying immunopathology. In some cases, an association of vasculitis with specific infectious agents has been reported; for example, polyarteritis nodosa (PAN) has been associated with hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV infections (1). However, it has been difficult to establish either causality or pathogenetic mechanisms, in part because of the low prevalence of vasculitis and the lack of good animal models (2). In this regard, while studying the chronic phase of C57BL/6J mice infected with the myotropic Colombiana strain of Trypanosoma cruzi, the infectious cause of Chagas' disease in humans, we noticed that the majority of animals developed hind limb paralysis associated with severe systemic necrotizing vasculitis affecting arteries and arterioles in skeletal muscle. Lesions were also present in many other tissues. A review of the literature identified several studies from 1970 to 2000 that described perivascular inflammation and frank arteritis in chronically T. cruzi-infected mouse skeletal muscle, aorta, nerves, and heart (3-9); however, the underlying immunologic mechanisms of disease were not defined. Interestingly, Okumura et al. reported necrotizing arteritis in small arteries beneath the peritoneal lining of the bowel and, occasionally, of the aorta and coronary arteries of T. cruzi-infected mice, which was at that time interpreted as "allergic necrotizing angiitis" (10). Dias et al. reported obliterative changes of the small and medium-sized branches of coronary...

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Section: Discussionsupporting

confidence: 92%

Trypanosoma cruzi Causes Paralyzing Systemic Necrotizing Vasculitis Driven by Pathogen-Specific Type I Immunity in Mice

et al. 2016

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“…In this study the large increase in keratinocyte hyperplasia was correlated with the increase of caspase 3 activation in hair follicle cells. Other studies by Nagajyothi et al (2006) showed that upon infection by a parasite, the amount of caveolin-1 decreases affected the functions of the receptor. Galbiati et al (2001) also observed that caveolin-1 can cause the cell to stay in the G0/G1 stage.…”

Section: Discussionmentioning

confidence: 90%

The Dog Mite,Demodex canis: Prevalence, Fungal Co-Infection, Reactions to Light, and Hair Follicle Apoptosis

Tsai

Chung

Wang

et al. 2011

Journal of Insect Science

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Infection rate, reaction to light, and hair follicle apoptosis are examined in the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013) prevalence of D. canis infection. Infection during the investigation peaked each winter, with an average prevalence of 12.5% (32/255). The infection rates significantly varied in accordance with month, sex, age, and breed (p < 0.05). Most of the lesions were discovered on the backs of the infected animals, where the infection rate was 52.1% (38/73) (P < 0.05). The epidemiologic analysis of infection based on landscape area factor, found that employing a map-overlapping method showed a higher infection rate in the eastern distribution of Taiwan's northern area than other areas. Isolation tests for Microsporum canis Bodin (Onygenales: Arthrodermataceae) and Trichophyton mentagrophyte Robin (Blanchard) on the D. canis infected dogs revealed prevalence rates of 4.4% (2/45) and 2.2% (1/45), respectively. Observations demonstrated that D. canis slowly moved from a light area to a dark area. Skin samples were examined for cellular apoptosis by activated caspase3 immunohistochemical staining. Cells that surrounded the infected hair follicles were activated caspase3-positive, revealing cell apoptosis in infected follicles via the activation of caspase3.

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“…Mice and cultured myoblasts infected with T. cruzi display increased expression of ERK and cyclin D1 [122,123], as well as of ERK activator protein 1 (AP-1) and NFκB, and a reduced expression of Cav-1 and Cav-3 [124,125]. The protein caveolin (Cav) is a negative regulator of both ERK and cyclin D1 [126].…”

Section: Innate Immunity To T Cruzi Infection: Experimental Studiesmentioning

confidence: 99%

Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease

et al. 2012

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Chagas disease caused by Trypanosoma cruzi remains an important neglected tropical disease and a cause of significant morbidity and mortality. No longer confined to endemic areas of Latin America, it is now found in non-endemic areas due to immigration. The parasite may persist in any tissue, but in recent years there has been increased recognition of adipose tissue both as an early target of infection and a reservoir of chronic infection. The major complications of this disease are cardiomyopathy and megasyndromes involving the gastrointestinal tract. The pathogenesis of Chagas disease is complex and multifactorial involving many interactive pathways. The significance of innate immunity, including the contributions of cytokines, chemokines, reactive oxygen species, and oxidative stress, has been emphasized. The role of the components of the eicosanoid pathway such as thromboxane A2 and the lipoxins has been demonstrated to have profound effects as both pro-and anti-inflammatory factors. Additionally, we discuss the vasoconstrictive actions of thromboxane A2 and endothelin-1n Chagas disease. Human immunity to T. cruzi infection and its role in pathogen control and disease progression have not been fully investigated. However, recently, it was demonstrated that a reduction in the anti-inflammatory cytokine IL-10 was associated with clinically significant chronic chagasic cardiomyopathy.

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Cyclin and Caveolin Expression in an Acute Model of Murine Chagasic Myocarditis

Cited by 26 publications

References 39 publications

Trypanosoma cruzi Causes Paralyzing Systemic Necrotizing Vasculitis Driven by Pathogen-Specific Type I Immunity in Mice

Trypanosoma cruzi Causes Paralyzing Systemic Necrotizing Vasculitis Driven by Pathogen-Specific Type I Immunity in Mice

The Dog Mite,Demodex canis: Prevalence, Fungal Co-Infection, Reactions to Light, and Hair Follicle Apoptosis

Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease

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