A multi-parametric analysis of Trypanosoma cruzi infection: common pathophysiologic patterns beyond extreme heterogeneity of host responses
Abstract 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 diffe...
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2017
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oai:doaj.org-article:8e3114f5db514579aa2a01d6f50a88a72021-12-02T16:05:59ZA multi-parametric analysis of Trypanosoma cruzi infection: common pathophysiologic patterns beyond extreme heterogeneity of host responses10.1038/s41598-017-08086-82045-2322https://doaj.org/article/8e3114f5db514579aa2a01d6f50a88a72017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08086-8https://doaj.org/toc/2045-2322Abstract 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.Julien Santi-RoccaFernando Fernandez-CortesCarlos Chillón-MarinasMaría-Luisa González-RubioDavid MartinNúria GironèsManuel FresnoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
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Medicine R Science Q Julien Santi-Rocca Fernando Fernandez-Cortes Carlos Chillón-Marinas María-Luisa González-Rubio David Martin Núria Gironès Manuel Fresno A multi-parametric analysis of Trypanosoma cruzi infection: common pathophysiologic patterns beyond extreme heterogeneity of host responses |
| description |
Abstract 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. |
| format |
article |
| author |
Julien Santi-Rocca Fernando Fernandez-Cortes Carlos Chillón-Marinas María-Luisa González-Rubio David Martin Núria Gironès Manuel Fresno |
| author_facet |
Julien Santi-Rocca Fernando Fernandez-Cortes Carlos Chillón-Marinas María-Luisa González-Rubio David Martin Núria Gironès Manuel Fresno |
| author_sort |
Julien Santi-Rocca |
| title |
A multi-parametric analysis of Trypanosoma cruzi infection: common pathophysiologic patterns beyond extreme heterogeneity of host responses |
| title_short |
A multi-parametric analysis of Trypanosoma cruzi infection: common pathophysiologic patterns beyond extreme heterogeneity of host responses |
| title_full |
A multi-parametric analysis of Trypanosoma cruzi infection: common pathophysiologic patterns beyond extreme heterogeneity of host responses |
| title_fullStr |
A multi-parametric analysis of Trypanosoma cruzi infection: common pathophysiologic patterns beyond extreme heterogeneity of host responses |
| title_full_unstemmed |
A multi-parametric analysis of Trypanosoma cruzi infection: common pathophysiologic patterns beyond extreme heterogeneity of host responses |
| title_sort |
multi-parametric analysis of trypanosoma cruzi infection: common pathophysiologic patterns beyond extreme heterogeneity of host responses |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/8e3114f5db514579aa2a01d6f50a88a7 |
| work_keys_str_mv |
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