Local association of<i>Trypanosoma cruzi</i>chronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale

Khan, Archie A.; Langston, Harry C; Costa, Fernanda Cristina; Olmo, F.J.; Taylor, Martin C.; McCann, Conor; Kelly, John M.; Lewis, Michael D.

doi:10.1101/2021.03.09.434577

Cited by 3 publications

(1 citation statement)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mice, however, are by far the most widely used species; in most cases they develop inflammatory cardiomyopathy and a few models are suitable for studying aspects of digestive disease. The compatibility of murine models with technologies such as bioluminescence imaging (BLI), which enable real-time monitoring of infections, is a major advantage and has led to significant advances in understanding how spatio-temporal infection dynamics relate to pathology development (8)(9)(10). Mice have been less well developed as models of advanced digestive megasyndromes, peripheral neuropathy or CNS infection, an important cause of acute mortality in human patients (11).…”

Section: Introductionmentioning

confidence: 99%

Dynamics ofTrypanosoma cruziinfection in hamsters and novel association with progressive motor dysfunction

Langston,

Francisco,

Doidge

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Chagas disease is a zoonosis caused by the protozoan parasiteTrypanosoma cruzi.Clinical outcomes range from long-term asymptomatic carriage to cardiac, digestive, neurological and composite presentations that can be fatal in both acute and chronic stages of the disease. Studies ofT. cruziin animal models, principally mice, have informed our understanding of the biological basis of this variability and its relationship to infection and host response dynamics. Hamsters have higher translational value for many human infectious diseases, but they have not been well developed as models of Chagas disease. We transposed a real-time bioluminescence imaging system forT. cruziinfection from mice into female Syrian hamsters (Mesocricetus auratus). This enabled us to study chronic tissue pathology in the context of spatiotemporal infection dynamics. Acute infections were widely disseminated, whereas chronic infections were almost entirely restricted to the skin and subcutaneous adipose tissue. Neither cardiac nor digestive tract disease were reproducible features of the model. Skeletal muscle had only sporadic parasitism in the chronic phase, but nevertheless displayed significant inflammation and fibrosis, features also seen in mouse models. Whereas mice had normal locomotion, all chronically infected hamsters developed hindlimb muscle hypertonia and a gait dysfunction resembling spastic diplegia. With further development, this model may therefore prove valuable in studies of peripheral nervous system involvement in Chagas disease.

show abstract

Section: Introductionmentioning

confidence: 99%

Dynamics ofTrypanosoma cruziinfection in hamsters and novel association with progressive motor dysfunction

Langston,

Francisco,

Doidge

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

The Potential Role of Microorganisms on Enteric Nervous System Development and Disease

2023

View full text Add to dashboard Cite

The enteric nervous system (ENS), the inherent nervous system of the gastrointestinal (GI) tract is a vast nervous system that controls key GI functions, including motility. It functions at a critical interface between the gut luminal contents, including the diverse population of microorganisms deemed the microbiota, as well as the autonomic and central nervous systems. Critical development of this axis of interaction, a key determinant of human health and disease, appears to occur most significantly during early life and childhood, from the pre-natal through to the post-natal period. These factors that enable the ENS to function as a master regulator also make it vulnerable to damage and, in turn, a number of GI-motility disorders. Increasing attention is now being paid to the potential of disruption of the microbiota and pathogenic microorganisms in the potential aetiopathogeneis of GI-motility disorders in children. This article explores the evidence regarding the relationship between the development and integrity of the ENS and the potential for such factors, notably dysbiosis and pathogenic bacteria, viruses and parasites, to impact upon them in early life.

show abstract

Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease

Francisco,

Sousa,

Vaughan

et al. 2023

Pathogens

Self Cite

View full text Add to dashboard Cite

Chronic Chagas cardiomyopathy (CCC) results from infection with the protozoan parasite Trypanosoma cruzi and is a prevalent cause of heart disease in endemic countries. We previously found that cardiac fibrosis can vary widely in C3H/HeN mice chronically infected with T. cruzi JR strain, mirroring the spectrum of heart disease in humans. In this study, we examined functional cardiac abnormalities in this host:parasite combination to determine its potential as an experimental model for CCC. We utilised electrocardiography (ECG) to monitor T. cruzi-infected mice and determine whether ECG markers could be correlated with cardiac function abnormalities. We found that the C3H/HeN:JR combination frequently displayed early onset CCC indicators, such as sinus bradycardia and right bundle branch block, as well as prolonged PQ, PR, RR, ST, and QT intervals in the acute stage. Our model exhibited high levels of cardiac inflammation and enhanced iNOS expression in the acute stage, but denervation did not appear to have a role in pathology. These results demonstrate the potential of the C3H/HeN:JR host:parasite combination as a model for CCC that could be used for screening new compounds targeted at cardiac remodelling and for examining the potential of antiparasitic drugs to prevent or alleviate CCC development and progression.

show abstract

Local association ofTrypanosoma cruzichronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale

Cited by 3 publications

References 42 publications

Dynamics ofTrypanosoma cruziinfection in hamsters and novel association with progressive motor dysfunction

Dynamics ofTrypanosoma cruziinfection in hamsters and novel association with progressive motor dysfunction

The Potential Role of Microorganisms on Enteric Nervous System Development and Disease

Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease

Contact Info

Product

Resources

About