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      Regulation of host immune cells and cytokine production induced by Trichinella spiralis infection Translated title: Régulation de la production des cellules immunitaires de l’hôte et des cytokines induite par l’infection par Trichinella spiralis

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          Abstract

          The nematode Trichinella spiralis can cause immunoregulation during the early phase of infection. However, previous studies are still insufficient for a full understanding of this phenomenon and its underlying mechanism. In this study, immune cells and cytokine profiles of T. spiralis infected mice were examined by Meso Scale Discovery (MSD) and flow cytometry. The MSD results of the spleen showed that Th1 immunity was inhibited from 6 h to 6 days post-infection (dpi) and the level of Th2 immune response was significantly increased at 6 dpi. The mesenteric lymph node showed a Th1/Th2 mixed immune response from 3 dpi to 6 dpi with a downtrend of Th1 at 6 dpi. Flow cytometry analysis showed that the proportion of Th1 cells of T cells was decreased significantly at 6 h after infection, the proportion of Th2 cells was markedly increased, indicating that Th1 immunity was significantly inhibited at 6 h after infection, and a hybrid immune response based on Th2 type was presented from 30 h to 6 dpi. The immunoregulation effects observed during this study have provided a better understanding of the development of the immune response induced by Trichinella infection.

          Translated abstract

          Le nématode Trichinella spiralis peut provoquer une immunorégulation pendant la phase précoce de l’infection. Cependant, les études précédentes sont encore insuffisantes pour bien comprendre ce phénomène et son mécanisme sous-jacent. Dans cette étude, les profils de cellules immunitaires et de cytokines de souris infectées par T. spiralis ont été examinés par DMÉ (Découverte à Méso-Échelle) et cytométrie de flux. Les résultats DMÉ de la rate ont montré que l’immunité Th1 était inhibée 6 h à 6 jours après l’infection (jai) et que le niveau de réponse immunitaire Th2 était augmenté de manière significative à 6 jai. Le ganglion mésentérique présentait une réponse immunitaire mixte Th1/Th2 de 3 à 6 jai avec une tendance à la baisse de Th1 à 6 jai. L’analyse par cytométrie en flux a montré que la proportion de lymphocytes T Th1 était significativement réduite 6 h après l’infection, que la proportion de Th2 était nettement augmentée, ce qui indiquait que l’immunité Th1 était significativement inhibée 6 h après l’infection, et qu’une réponse immunitaire hybride sur le type Th2 était présentée de 30 h à 6 jai. Les effets d’immunorégulation observés au cours de cette étude ont permis de mieux comprendre le développement de la réponse immunitaire induite par l’infection à Trichinella.

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          Most cited references 28

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          Regulatory T-Cells at the Interface between Human Host and Pathogens in Infectious Diseases and Vaccination

          Regulatory T-cells (Tregs) act at the interface of host and pathogen interactions in human infectious diseases. Tregs are induced by a wide range of pathogens, but distinct effects of Tregs have been demonstrated for different pathogens and in different stages of infection. Moreover, Tregs that are induced by a specific pathogen may non-specifically suppress immunity against other microbes and parasites. Thus, Treg effects need to be assessed not only in homologous but also in heterologous infections and vaccinations. Though Tregs protect the human host against excessive inflammation, they probably also increase the risk of pathogen persistence and chronic disease, and the possibility of disease reactivation later in life. Mycobacterium leprae and Mycobacterium tuberculosis, causing leprosy and tuberculosis, respectively, are among the most ancient microbes known to mankind, and are master manipulators of the immune system toward tolerance and pathogen persistence. The majority of mycobacterial infections occur in settings co-endemic for viral, parasitic, and (other) bacterial coinfections. In this paper, we discuss recent insights in the activation and activity of Tregs in human infectious diseases, with emphasis on early, late, and non-specific effects in disease, coinfections, and vaccination. We highlight mycobacterial infections as important models of modulation of host responses and vaccine-induced immunity by Tregs.
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            Analysis of differentially expressed genes of Trichinella spiralis larvae activated by bile and cultured with intestinal epithelial cells using real-time PCR.

            The activation of Trichinella spiralis muscle larvae (ML) by exposure to intestinal contents or bile and the intestinal epithelial cells (IECs) themselves are two pivotal requirements for the in vitro larval invasion of IECs. However, it is yet unknown which genes are involved in the process of larval invasion. The purpose of the present study was to analyze the differentially expressed genes of T. spiralis larvae activated by bile and cultured with IECs by using real-time polymerase chain reaction. Ten T. spiralis genes encoded the proteins produced by the larvae after co-culture with IECs were selected. Compared with untreated ML, four genes were up-regulated in both bile-activated and cell-cultured larvae, including calcium-dependent secretion activator (Csa; 2.55- and 16.04-fold, respectively), multi cystatin-like domain protein precursor (Mcd; 4.36 and 52), serine protease (Sp; 2.03 and 20.02), and intermediate filament protein ifa-1 (Ifa 1; 2 and 3.31). The expression of two genes, enolase (Eno; 1.51) and ribosomal protein S6 kinase beta-1 (Rsk; 1.49), was up-regulated only in cell-cultured larvae, not in bile-activated larvae. The expression of secreted 5'-nucleotidase (5 N; 1.42) and putative serine protease (Psp; 1.41) was up-regulated in bile-activated larvae, but was not changed or down-regulated after cultured with IECs. ATP synthase F1, beta subunit (ATPase; 0.58 and 0.51) and serine protease precursor (Spp; 0.42 and 0.65) were down-regulated in both bile-activated and cell-cultured larvae. This study provide some differentially expressed genes among the untreated (normal), bile-activated and cell-cultured larvae of T. spiralis. The up-regulated genes might be related with the larval invasion of IECs, but their exact biological functions need to be further investigated. This study will be helpful to further elucidate the molecular mechanism of the invasion of IECs by T. spiralis larvae and to better understand the interaction between parasite and host enterocytes.
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              Coordinated control of immunity to muscle stage Trichinella spiralis by IL-10, regulatory T cells, and TGF-beta.

              We previously demonstrated that IL-10 is critical in the control of acute inflammation during development of Trichinella spiralis in the muscle. In this study, we use gene-targeted knockout mice, adoptive transfer of specific T cell populations, and in vivo Ab treatments to determine the mechanisms by which inflammation is controlled and effector T cell responses are moderated during muscle infection. We report that CD4(+)CD25(-) effector T cells, rather than CD4(+)CD25(+) regulatory T cells, suppress inflammation by an IL-10-dependent mechanism that limits IFN-gamma production and local inducible NO synthase induction. Conversely, we show that depletion of regulatory T cells during infection results in exaggerated Th2 responses. Finally, we provide evidence that, in the absence of IL-10, TGF-beta participates in control of local inflammation in infected muscle and promotes parasite survival.
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                Author and article information

                Journal
                Parasite
                Parasite
                parasite
                Parasite
                EDP Sciences
                1252-607X
                1776-1042
                2019
                19 December 2019
                : 26
                : ( publisher-idID: parasite/2019/01 )
                Affiliations
                [1 ] College of Animal Science and Technology, Inner Mongolia University for Nationalities Inner Mongolia 028042 Tongliao PR China
                [2 ] Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis/College of Veterinary Medicine, Jilin University 130000 Changchun PR China
                [3 ] Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou Jiangsu PR China
                Author notes
                [a]

                These authors contributed equally to this work.

                Article
                parasite190098 10.1051/parasite/2019074
                10.1051/parasite/2019074
                6921962
                31855175
                © Y. Song et al., published by EDP Sciences, 2019

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 7, Tables: 0, Equations: 0, References: 29, Pages: 7
                Categories
                Research Article

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