A multi-parametric analysis of Trypanosoma cruzi infection: common pathophysiologic patterns beyond extreme heterogeneity of host responses

Santi-Rocca, J., Fernandez-Cortes, F., Chillón-Marinas, C., González-Rubio, M.-L., Martin, D., Gironès, N. and Fresno, M. (2017) A multi-parametric analysis of Trypanosoma cruzi infection: common pathophysiologic patterns beyond extreme heterogeneity of host responses. Scientific Reports, 7, 8893. (doi: 10.1038/s41598-017-08086-8) (PMID:28827716) (PMCID:PMC5566495)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Fernandez-Cortes, Dr Fernando
• Authors: Santi-Rocca, J., Fernandez-Cortes, F., Chillón-Marinas, C., González-Rubio, M.-L., Martin, D., Gironès, N., and Fresno, M.
• Subjects: Q Science > QH Natural history > QH301 Biology; Q Science > QR Microbiology > QR180 Immunology
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Scientific Reports 7: 8893
• Publisher Policy: Reproduced under a Creative Commons license