Interaction of Signaling Lymphocytic Activation Molecule Family 1 (SLAMF1) receptor with Trypanosoma cruzi is strain-dependent and affects NADPH oxidase expression and activity
| العنوان: | Interaction of Signaling Lymphocytic Activation Molecule Family 1 (SLAMF1) receptor with Trypanosoma cruzi is strain-dependent and affects NADPH oxidase expression and activity |
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| المؤلفون: | Francisco Callejas-Hernández, Jesús Osuna-Pérez, Konstantinos Stamatakis, María C. Maza, Carlos Chillón-Marinas, Cristina Poveda, Núria Gironès, Jossela Calderón, Manuel Fresno, Alfonso Herreros-Cabello |
| المساهمون: | Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Red de Investigación Cooperativa en Enfermedades Tropicales (España) |
| المصدر: | PLoS Neglected Tropical Diseases Digital.CSIC. Repositorio Institucional del CSIC instname PLoS Neglected Tropical Diseases, Vol 14, Iss 9, p e0008608 (2020) |
| بيانات النشر: | Public Library of Science, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, CD4-Positive T-Lymphocytes, RC955-962, Gene Expression, CD8-Positive T-Lymphocytes, Parasite load, Parasite Load, White Blood Cells, Mice, 0302 clinical medicine, Medical Conditions, Mathematical and Statistical Techniques, Signaling Lymphocytic Activation Molecule Family Member 1, Animal Cells, Arctic medicine. Tropical medicine, Gene expression, Chlorocebus aethiops, Medicine and Health Sciences, Receptor, Protozoans, Trypanosoma Cruzi, Mice, Knockout, Principal Component Analysis, Mice, Inbred BALB C, NADPH oxidase, biology, Statistics, Eukaryota, Heart, Infectious Diseases, Physical Sciences, NADPH Oxidase 2, Disease Susceptibility, Public aspects of medicine, RA1-1270, Cellular Types, Anatomy, Research Article, Trypanosoma, Immune Cells, 030231 tropical medicine, Immunology, Research and Analysis Methods, Parasite Replication, Proinflammatory cytokine, Cell Line, 03 medical and health sciences, Immune system, Parasitic Diseases, Genetics, Animals, Humans, Chagas Disease, Statistical Methods, Trypanosoma cruzi, Vero Cells, Blood Cells, Macrophages, Myocardium, Public Health, Environmental and Occupational Health, Organisms, Biology and Life Sciences, Cell Biology, Dendritic Cells, biology.organism_classification, Molecular biology, Parasitic Protozoans, Gastrointestinal Tract, 030104 developmental biology, HEK293 Cells, Multivariate Analysis, biology.protein, Cardiovascular Anatomy, Parasitology, Reactive Oxygen Species, Digestive System, CD8, Mathematics |
| الوصف: | The receptor Signaling Lymphocyte-Activation Molecule Family 1 (SLAMF1) controls susceptibility to Infection by the lethal Trypanosoma cruzi Y strain. To elucidate whether genetic diversity of the parasite was related with disease susceptibility, we further analyzed the role of SLAMF1 using 6 different Trypanosoma cruzi strains including Y. The interaction of SLAMF1 receptor with T. cruzi was evidenced by fluorescence microscopy, flow cytometry and quantitative PCR. All the strains, except VFRA, showed a decrease in parasite load in infected macrophages in Slamf1-/- compared to BALB/c. In macrophages gene expression NADPH oxidase (NOX2), and reactive oxygen species (ROS) production increased in Slamf1-/- compared to BALB/c in 5 out of 6 strains. However, Slamf1-/-macrophages infected with VFRA strain exhibited a divergent behavior, with higher parasite load, lower NOX2 expression and ROS production compared to BALB/c. Parasitological and immunological studies in vivo with Y strain showed that in the absence of SLAMF1 the immune response protected mice from the otherwise lethal Y infection favoring a proinflammatory response likely involving CD4, CD8, dendritic cells and classically activated macrophages. In the case of VFRA, no major changes were observed in the absence of SLAMF1. Thus, the results suggest that the T. cruzi affects SLAMF1-dependent ROS production, controlling parasite replication in macrophages and affecting survival in mice in a strain-dependent manner. Further studies will focus in the identification of parasite molecules involved in SLAMF1 interaction to explain the immunopathogenesis of the disease. Author summary Chagas disease, caused by Trypanosoma cruzi, is characterized by an acute phase, with low mortality, and after many years without any sign of disease, patients develop a symptomatic chronic phase, characterized by cardiomyopathy and/or digestive mega syndromes. These differences have been attributed to the high genetic variability of this parasite. We have shown that the receptor Signaling Lymphocyte-Activation Molecule Family 1 (SLAMF1) controls susceptibility to Infection by the lethal T. cruzi Y strain. Here we studied in detail the immunopathogenic role of SLAMF1 using 6 genetically diverse strains of T. cruzi using in vitro and in vivo approaches. Our results indicate an important role of SLAMF1 in T. cruzi infection which is parasite strain-dependent. We found that parasites interact with SLAMF1 in macrophages affecting NADPH oxidase (NOX2) expression and reactive oxygen species (ROS) production 5 out of 6 strains tested. Y and VFRA strains showed a divergent behavior in vitro and the role of SLAMF1 in the in vivo infection was also strikingly different. The Y strain caused 70% mortality in BALB/c mice but not in Slamf1-/- mice. The proinflammatory response was stronger in the last, suggesting that SLAMF1 was repressing protective immune responses of mice infected with the Y strain. In contrast, for VFRA, SLAMF1 deficiency resulted in 100% survival of BALB/c mice, without major changes in the immune response in the absence of SLAMF1. Thus, the results indicate that SLAMF1 receptor interacts with T. cruzi, affecting parasite replication and ROS production in macrophages as well as the adaptive immune response in mice in a parasite strain-dependent manner. Future studies will focus in understanding the immunopathogenic role of SLAMF1 during T. cruzi infection. |
| اللغة: | English |
| تدمد: | 1935-2735 1935-2727 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5e57a7358b0bf107123032e6ad1382c0Test http://europepmc.org/articles/PMC7515593Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5e57a7358b0bf107123032e6ad1382c0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19352735 19352727 |
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