A multi-parametric analysis of Trypanosoma cruzi infection: Common pathophysiologic patterns beyond extreme heterogeneity of host responses
Entity
UAM. Departamento de Biología Molecular; Centro de Biología Molecular Severo Ochoa (CBM); Instituto de Investigación del Hospital de La Princesa (IP)Publisher
Nature Publishing GroupDate
2017-08-21Citation
10.1038/s41598-017-08086-8
Scientific Reports 7 (2017): 8893
ISSN
2045-2322DOI
10.1038/s41598-017-08086-8Funded by
This work was supported by “Ministerio de Ciencia e Innovación” (SAF2013-42850-R); “Fondo de Investigaciones Sanitarias” (PI12/00289); “Red de Investigación de Centros de Enfermedades Tropicales” (RICET 2010RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet); “Universidad Autónoma de Madrid” and “Comunidad de Madrid” (CC08-UAM/SAL-4440/08); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD-2332) and “Fundación Ramón Areces”Project
Gobierno de España. SAF2013-42850-R; Gobierno de España. PI12/00289; info:eu-repo/grantAgreement/EC/FP7/22303; Comunidad de Madrid. S-2010/BMD-2332/INDISNETEditor's Version
http://dx.doi.org/10.1038/s41598-017-08086-8Subjects
Trypanosoma cruzi; Pathophysiogenesis; Parasite strains; Infection phase; Multi-parametric analysis; Biología y Biomedicina / BiologíaRights
© The Author(s) 2017Abstract
The extreme genetic diversity of the protozoan Trypanosoma cruzi has been proposed to be associated with the clinical outcomes of the disease it provokes: Chagas disease (CD). To address this question, we analysed the similarities and differences in the CD pathophysiogenesis caused by different parasite strains. Using syngeneic mice infected acutely or chronically with 6 distant parasite strains, we integrated simultaneously 66 parameters: parasite tropism (7 parameters), organ and immune responses (local and systemic; 57 parameters), and clinical presentations of CD (2 parameters).
While the parasite genetic background consistently impacts most of these parameters, they remain highly variable, as observed in patients, impeding reliable one-dimensional association with phases, strains, and damage. However, multi-dimensional statistics overcame this extreme intra-group variability for each individual parameter and revealed some pathophysiological patterns that accurately allow defining (i) the infection phase, (ii) the infecting parasite strains, and (iii) organ damage type and intensity. Our results demonstrated a greater variability of clinical outcomes and host responses to T. cruzi infection than previously thought, while our multi- parametric analysis defined common pathophysiological patterns linked to clinical outcome of CD, conserved among the genetically diverse infecting strains
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Google Scholar:Santi-Rocca, Julien
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Fernández-Cortés, Fernando
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Chillón-Marinas, Carlos
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González-Rubio, María-Luisa
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Martín, David
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Gironés Pujol, Nuria
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Fresno Escudero, Manuel
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