Journal Article

Transcriptional Profiles of Cytokine/Chemokine Factors of Immune Cell-Homing to the Parasitic Lesions: A Comprehensive One-Year Course Study in the Liver of E. multilocularis-Infected Mice

Gottstein, Bruno, Lü, Guodong, Lin, Renyong, Li, Liang, Wang, Junhua, Vuitton, Dominique A., Zhang, Wenbao, Blagosklonov, Oleg, Zhang, Chuangshan, Wen, Hao, Lu, Xiaomei

2014

Overview

Pathogenesis of chronically developing alveolar echinococcosis (AE) is characterized by a continuous, granulomatous, periparasitic infiltration of immune cells surrounding the metacestode of Echinococcus multilocularis (E.multilocularis) in the affected liver. A detailed cytokine and chemokine profile analysis of the periparasitic infiltrate in the liver has, however, not yet been carried out in a comprehensive way all along the whole course of infection in E. multilocularis intermediate hosts. We thus assessed the hepatic gene expression profiles of 18 selected cytokine and chemokine genes using qRT-PCR in the periparasitic immune reaction and the subsequent adjacent, not directly affected, liver tissue of mice from day 2 to day 360 post intra-hepatic injection of metacestode. DNA microarray analysis was also used to get a more complete picture of the transcriptional changes occurring in the liver surrounding the parasitic lesions. Profiles of mRNA expression levels in the hepatic parasitic lesions showed that a mixed Th1/Th2 immune response, characterized by the concomitant presence of IL-12α, IFN-γ and IL-4, was established very early in the development of E. multilocularis. Subsequently, the profile extended to a combined tolerogenic profile associating IL-5, IL-10 and TGF-β. IL-17 was permanently expressed in the liver, mostly in the periparasitic infiltrate; this was confirmed by the increased mRNA expression of both IL-17A and IL-17F from a very early stage, with a subsequent decrease of IL-17A after this first initial rise. All measured chemokines were significantly expressed at a given stage of infection; their expression paralleled that of the corresponding Th1, Th2 or Th17 cytokines. In addition to giving a comprehensive insight in the time course of cytokines and chemokines in E. multilocularis lesion, this study contributes to identify new targets for possible immune therapy to minimize E. multilocularis-related pathology and to complement the only parasitostatic effect of benzimidazoles in AE.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Alveoli / Analysis / Animal tissues / Animals / Benzimidazoles / Biology and Life Sciences / Chemokines / Chemokines - genetics / Cytokines / Cytokines - genetics / Deoxyribonucleic acid / Disease / DNA / DNA microarrays / Echinococcosis / Echinococcosis, Hepatic - genetics / Echinococcosis, Hepatic - immunology / Echinococcosis, Hepatic - parasitology / Echinococcosis, Hepatic - pathology / Echinococcus granulosus / Echinococcus multilocularis / Echinococcus multilocularis - immunology / Female / Gene expression / Gene Expression Profiling / Genetic aspects / Genetic research / Health aspects / Helper cells / Homing / Hospitals / Immune response / Immune system / Immunity / Immunity, Innate / Immunotherapy / Infection / Infections / Infiltration / Inflammation - genetics / Inflammation - immunology / Inflammation - parasitology / Inflammation Mediators - metabolism / Interferon / Interleukin 10 / Interleukin 17 / Interleukin 4 / Interleukin 5 / Laboratories / Lesions / Liver / Lymphocytes / Lymphocytes T / Medical research / Medicine and Health Sciences / Mice / Parasites / Parasitic diseases / Parasitology / Pathogenesis / Research and Analysis Methods / RNA / RNA, Messenger - genetics / Rodents / Schistosoma mansoni / Studies / T-Lymphocytes, Regulatory - immunology / T-Lymphocytes, Regulatory - metabolism / Target recognition / Th1 Cells - immunology / Th1 Cells - metabolism / Th17 Cells - immunology / Th17 Cells - metabolism / Th2 Cells - immunology / Th2 Cells - metabolism / Transcription / Transcription (Genetics) / Transcription Factors - genetics / Transcription Factors - metabolism / Transcriptome / Transforming growth factors / γ-Interferon