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      Transcriptome Profiling Reveals Th17-Like Immune Responses Induced in Zebrafish Bath-Vaccinated with a Live Attenuated Vibrio anguillarum

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          Abstract

          Background

          A candidate vaccine, live attenuated Vibrio anguillarum developed in our laboratory could prevent vibriosis of fish resulted from V. anguillarum and V. alginolyticus. To elucidate the molecular mechanisms underlying the vaccine protection, we used microarray technology to compare the spleen transcriptomes of bath-vaccinated and unvaccinated zebrafish at 28 days post vaccination.

          Principal Findings

          A total of 2164 genes and transcripts were differentially expressed, accounting for 4.9% of all genes represented on the chip. In addition to iron metabolism related to the innate immunity and the signaling pathways, these differentially expressed genes also involved in the adaptive immunity, mainly including the genes associated with B and T cells activation, proliferation and expansion. Transcription profiles of Th17-related transcription factors, cytokines and cytokine receptors during 35 days post-vaccination implied that Th17 cells be activated in bath-vaccinated zebrafish.

          Conclusion/Significance

          The transcriptome profiling with microarray revealed the Th17-like immune response to bath-vaccination with the live attenuated V. anguillarum in zebrafish.

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          Most cited references34

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          Requirement of Interleukin 17 Receptor Signaling for Lung Cxc Chemokine and Granulocyte Colony-Stimulating Factor Expression, Neutrophil Recruitment, and Host Defense

          Bacterial pneumonia is an increasing complication of HIV infection and inversely correlates with the CD4+ lymphocyte count. Interleukin (IL)-17 is a cytokine produced principally by CD4+ T cells, which induces granulopoiesis via granulocyte colony-stimulating factor (G-CSF) production and induces CXC chemokines. We hypothesized that IL-17 receptor (IL-17R) signaling is critical for G-CSF and CXC chemokine production and lung host defenses. To test this, we used a model of Klebsiella pneumoniae lung infection in mice genetically deficient in IL-17R or in mice overexpressing a soluble IL-17R. IL-17R–deficient mice were exquisitely sensitive to intranasal K. pneumoniae with 100% mortality after 48 h compared with only 40% mortality in controls. IL-17R knockout (KO) mice displayed a significant delay in neutrophil recruitment into the alveolar space, and had greater dissemination of K. pneumoniae compared with control mice. This defect was associated with a significant reduction in steady-state levels of G-CSF and macrophage inflammatory protein (MIP)-2 mRNA and protein in the lung in response to the K. pneumoniae challenge in IL-17R KO mice. Thus, IL-17R signaling is critical for optimal production of G-CSF and MIP-2 and local control of pulmonary K. pneumoniae infection. These data support impaired IL-17R signaling as a potential mechanism by which deficiency of CD4 lymphocytes predisposes to bacterial pneumonia.
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            The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo.

            Interleukin 23 (IL-23) is required for autoimmune inflammation mediated by IL-17-producing helper T cells (T(H)-17 cells) and has been linked to many human immune disorders. Here we restricted deficiency in the IL-23 receptor to defined cell populations in vivo to investigate the requirement for IL-23 signaling in the development and function of T(H)-17 cells in autoimmunity, inflammation and infection. In the absence of IL-23, T(H)-17 development was stalled at the early activation stage. T(H)-17 cells failed to downregulate IL-2 and also failed to maintain IL-17 production or upregulate expression of the IL-7 receptor alpha-chain. These defects were associated with less proliferation; consequently, fewer effector T(H)-17 cells were produced in the lymph nodes and hence available to emigrate to the bloodstream and tissues.
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              Induction and effector functions of T(H)17 cells.

              T helper (T(H)) cells constitute an important arm of the adaptive immune system because they coordinate defence against specific pathogens, and their unique cytokines and effector functions mediate different types of tissue inflammation. The recently discovered T(H)17 cells, the third subset of effector T helper cells, have been the subject of intense research aimed at understanding their role in immunity and disease. Here we review emerging data suggesting that T(H)17 cells have an important role in host defence against specific pathogens and are potent inducers of autoimmunity and tissue inflammation. In addition, the differentiation factors responsible for their generation have revealed an interesting reciprocal relationship with regulatory T (T(reg)) cells, which prevent tissue inflammation and mediate self-tolerance.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                4 September 2013
                : 8
                : 9
                : e73871
                Affiliations
                [1]State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
                Beijing Institute of Microbiology and Epidemiology, China
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: HW QL QW YZ. Performed the experiments: HZ CF. Analyzed the data: HZ CF. Contributed reagents/materials/analysis tools: HZ CF MY. Wrote the paper: HZ HW YZ.

                Article
                PONE-D-13-07807
                10.1371/journal.pone.0073871
                3762715
                24023910
                095ac4d3-e58f-4d8c-ae08-2afd4fe15b00
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 February 2013
                : 24 July 2013
                Page count
                Pages: 11
                Funding
                This work was supported by grants from the National Natural Science Foundation of China (No. 31001121, http://www.nsfc.gov.cn/Portal0/default166.htm), Program for New Century Excellent Talents in University (No. Ncet-09-0344, http://www.dost.moe.edu.cn/) and the Shanghai Leading Academic Discipline Project 278 (No. B505, http://www.shec.edu.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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