Multiplex profiling of inflammation-related bioactive lipid mediators in Toxocara canis- and Toxocara cati-induced neurotoxocarosis
| العنوان: | Multiplex profiling of inflammation-related bioactive lipid mediators in Toxocara canis- and Toxocara cati-induced neurotoxocarosis |
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| المؤلفون: | Patrick Waindok, Elisabeth Janecek-Erfurth, Dimitri Lindenwald, Esther Wilk, Klaus Schughart, Robert Geffers, Laurence Balas, Thierry Durand, Katharina Maria Rund, Nils Helge Schebb, Christina Strube |
| المساهمون: | Research Group Genome Analytics [Braunschweig], Helmholtz Centre for Infection Research (HZI), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. |
| المصدر: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Public Library of Science, 2019, 13 (9), pp.e0007706. ⟨10.1371/journal.pntd.0007706⟩ PLoS neglected tropical diseases PLoS Neglected Tropical Diseases, Vol 13, Iss 9, p e0007706 (2019) |
| بيانات النشر: | HAL CCSD, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Life Cycles, Docosahexaenoic Acids, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, RC955-962, Immunology, Pathology and Laboratory Medicine, Biochemistry, Mice, Lipid Mediators, Signs and Symptoms, Larvae, Diagnostic Medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Arctic medicine. Tropical medicine, Cerebellum, Metabolites, Medicine and Health Sciences, Animals, Humans, Oxylipins, Cerebrum, Immune Response, Brain Chemistry, Cerebral Cortex, Inflammation, Brain Diseases, Toxocariasis, Brain, Toxocara canis, Biology and Life Sciences, Lipids, Mice, Inbred C57BL, Metabolism, Larva, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Metabolic Pathways, Public aspects of medicine, RA1-1270, Inflammation Mediators, Anatomy, Research Article, Developmental Biology |
| الوصف: | Background Somatic migration of Toxocara canis- and T. cati-larvae in humans may cause neurotoxocarosis (NT) when larvae accumulate and persist in the central nervous system (CNS). Host- or parasite-induced immunoregulatory processes contribute to the pathogenesis; however, detailed data on involvement of bioactive lipid mediators, e.g. oxylipins or eico-/docosanoids, which are involved in the complex molecular signalling network during infection and inflammation, are lacking. Methodology/Principal findings To elucidate if T. canis- and T. cati-induced NT affects the homeostasis of oxylipins during the course of infection, a comprehensive lipidomic profiling in brains (cerebra and cerebella) of experimentally infected C57BL/6J mice was conducted at six different time points post infection (pi) by liquid-chromatography coupled to electrospray tandem mass spectrometry (LC-ESI-MS/MS). Only minor changes were detected regarding pro-inflammatory prostaglandins (cyclooxygenase pathway). In contrast, a significant increase of metabolites resulting from lipoxygenase pathways was observed for both infection groups and brain regions, implicating a predominantly anti-inflammatory driven immune response. This observation was supported by a significantly increased 13-hydroxyoctadecadienoic acid (HODE)/9-HODE ratio during the subacute phase of infection, indicating an anti-inflammatory response to neuroinfection. Except for the specialised pro-resolving mediator (SPM) neuroprotectin D1 (NPD1), which was detected in mice infected with both pathogens during the subacute phase of infection, no other SPMs were detected. Conclusions/Significance The obtained results demonstrate the influence of Toxocara spp. on oxylipins as part of the immune response of the paratenic hosts. Furthermore, this study shows differences in the alteration of the oxylipin composition between T. canis- and T. cati-brain infection. Results contribute to a further understanding of the largely unknown pathogenesis and mechanisms of host-parasite interactions during NT. Author summary Neurotoxocarosis (NT) is induced by larvae of the zoonotic roundworms Toxocara canis and T. cati migrating and persisting in the central nervous system of paratenic hosts, and may be accompanied by severe neurological symptoms. Toxocara spp. are known to modulate the hosts’ immune response, but data concerning involvement of signalling molecules are lacking. An important class of mediators participating in the complex molecular signalling network during infection and inflammation are bioactive regulatory lipids, derived from arachidonic acid and other polyunsaturated fatty acids. For a better understanding of inflammatory processes in the brain during an infection with Toxocara spp., a comprehensive analysis of regulatory lipids was conducted. The infection was predominantly characterised by only minor changes in the pattern of pro-inflammatory oxylipins, while anti-inflammatory metabolites, derived from lipoxygenase pathways, were significantly elevated in the subacute phase as well as in the beginning of the chronic phase of infection. This trend was also reflected in the 13-HODE/9-HODE ratio, a biomarker for the immunological status of an active infection. Obtained data provide a valuable insight in the host’s immune reaction as response against neuroinvasive Toxocara spp.-larvae, contributing to the characterisation of the mostly unknown pathogenesis of NT. |
| اللغة: | English |
| تدمد: | 1935-2727 1935-2735 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::26e0ebea4921923024ce51ee59dac67eTest https://hal.archives-ouvertes.fr/hal-02326889/file/Durand_04.pdfTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....26e0ebea4921923024ce51ee59dac67e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19352727 19352735 |
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