Systematic mapping of hearts from chronic chagasic patients: the association between the occurrence of histopathological lesions and<i>Trypanosoma cruzi</i>antigens

Palomino, Suely Aparecida Pinheiro; Aiello, Vera Demarchi; Higuchi, Maria de Lourdes

doi:10.1080/00034983.2000.11813580

Cited by 81 publications

(58 citation statements)

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“…Lesion severity correlates with parasite burden or the presence of parasite DNA (38)(39)(40); however, in Chagas' disease, as in our mouse model of T. cruzi-dependent systemic necrotizing vasculitis, the degrees of inflammation and organ destruction are highly disproportionate to the low parasite burden found in the chronic phase. Whether this level of parasite is sufficient to maintain chagasic immunopathology or instead requires recruitment of autoreactive responses following a parasite-induced break of tolerance is an important unanswered question.…”

Section: Discussionmentioning

confidence: 77%

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: Discussionmentioning

confidence: 77%

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

et al. 2016

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“…It is valuable to mention that several studies have clearly demonstrated a close association between the parasite persistence and the intensity of inflammatory processes and the severity of the histopathological lesions in the heart and digestive organs during the chronic phase of this infection, both in human (Palomino et al, 2000) and experimental models (Zhang and Tarleton, 1999). Interestingly, CD8…”

Section: Discussionmentioning

confidence: 99%

Tumour necrosis factor (TNF)-mediated NF-κB activation facilitates cellular invasion of non-professional phagocytic epithelial cell lines by Trypanosoma cruzi

Pinto

Sales

Camargos

et al. 2011

Cellular Microbiology

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SummaryAt the site of infection, pro-inflammatory cytokines locally produced by macrophages infected with Trypanosoma cruzi can activate surrounding nonprofessional phagocytes such as fibroblasts, epithelial and endothelial cells, which can be further invaded by the parasite. The effect of secreted soluble factors on the invasion of these cells remains, however, to be established. We show here that two epithelial cell lines become significantly susceptible to the infection by the Y strain of T. cruzi after tumour necrosis factor (TNF) treatment. The increase in the invasion was correlated with the increasing concentration of recombinant TNF added to cultures of HEK293T or LLC-MK2 cells. Supernatants taken from PMA-differentiated human monocytes infected with T. cruzi also increased the permissiveness of epithelial cells to subsequent infection with the parasite, which was inhibited by a TNF monoclonal antibody. Furthermore, the permissiveness induced by TNF was inhibited by TPCK, and led to significant decrease in the number of intracellular parasites, providing evidence that activation of NF-kB induced by TNF favours the invasion of the epithelial cell lines by T. cruzi through yet an unidentified mechanism. Our data indicate that soluble factors released from macrophages early in the infection favours T. cruzi invasion of non-professional phagocytic cells.

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“…Several studies have demonstrated that T. cruzi parasites or antigens can be found, although rarely, in individuals with chronic infection (Barbosa Jr andAndrade 1984, Jones et al 1993, Palomino et al 2000). However, the analyses of human heart fragments have failed to show a correlation between intensity of inflammation and of parasitism, even with the use of highly sensitive techniques, such as PCR or immunohistochemistry (Palomino et al 2000, Olivares-Villagomez et al 1998. In fact, this remarkable feature of the disease was immediately pointed out 90 years ago by Vianna (1911), the excellent pathologist working in collaboration with Carlos Chagas.…”

Section: Parasite Persistence and Inflammationmentioning

confidence: 99%

The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

Soares

Pontes-de-Carvalho

Ribeiro-dos-Santos

2001

An. Acad. Bras. Ciênc.

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Chagas' disease is a major health problem in Latin America, where it constitutes one of the leading causes of heart failure. About one fourth of Trypanosoma cruzi-infected individuals develop chronic chagasic cardiomyopathy (CChC), the most severe form of the disease. CChC is histologically characterized by the presence of multifocal inflammatory infiltrates in the heart, composed mainly by mononuclear cells, usually adhered to myocytes and leading to myocytolysis, and frequently by interstitial fibrosis. The pathogenesis of CChC is still unclear, despite intense investigations both in human beings and in animal models of the disease. Although tissue parasitism is rare in the chronic phase of infection, an immune response targeted to persistent parasites or parasite antigens is suggested, by some authors, as the pathogenic mechanism of CChC. Other researchers affirm that the lack of correlation between tissue parasitism and intensity of inflammation suggests, along with the presence of autoreactive immune responses, that CChC results from the action of an autoimmune response. Herein we review reports from the literature and our own data, which together indicate, on one hand, the participation of parasite-specific immune responses and, on the other hand, clearly demonstrate the participation of heart-specific immune responses in the pathogenesis of CChC. Moreover, multiple factors may determine whether an individual in the indeterminate form of the disease will develop CChC. The mechanisms by which T. cruzi breaks immunological tolerance to heart antigens are also discussed.

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Systematic mapping of hearts from chronic chagasic patients: the association between the occurrence of histopathological lesions andTrypanosoma cruziantigens

Cited by 81 publications

References 10 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

Tumour necrosis factor (TNF)-mediated NF-κB activation facilitates cellular invasion of non-professional phagocytic epithelial cell lines by Trypanosoma cruzi

The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

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