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      Production of Inflammatory Cytokines and Nitric Oxide by Human Mast Cells Incubated with Toxoplasma gondii Lysate

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          Abstract

          The roles of mast cells in allergic diseases and helminth infections are well known. However, the roles of mast cells in T. gondii infection is poorly understood. This study was focused on the production of pro-inflammatory cytokines (TNF-α, IL-4), chemokines (CXCL8, MCP-1) and nitric oxide (NO) by mast cells in response to soluble lysate of T. gondii tachyzoites. Production of CXCL8 (IL-8), MCP-1, TNF-α and IL-4 were measured by RT-PCR and ELISA. Western blot were used for detection of CXCR-1 and CXCR2. Our results showed that T. gondii lysates triggered mast cells to release CXCL8, MCP-1, TNF-α, IL-4 and to produce NO. This suggests that mast cells play an important role in inflammatory responses to T. gondii.

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          Dendritic cells expressing plasmacytoid marker PDCA-1 are Trojan horses during Toxoplasma gondii infection.

          Allison Bierly, William J Shufesky, Woraporn Sukhumavasi … (2008)
          Plasmacytoid dendritic cells (pDCs) play a key role in the innate immune response to viral infection, due largely to their ability to produce large quantities of type I IFNs. These cells are also notable for their ability to differentiate into conventional dendritic cells after appropriate stimulation. Here, we show that a splenic population of murine CD11c(+) cells expressing pDC markers Gr-1, B220, and PDCA-1 is preferentially parasitized after infection with the virulent RH strain of Toxoplasma gondii. Although these markers are closely associated with pDCs, the population we identified was unusual because the cells express CD11b and higher than expected levels of CD11c. By adoptive transfer of CD45.1-positive cells into CD45.2 congenic mice, we show that CD11c(+)Gr-1(+) cells migrate from the peritoneal cavity to the spleen. During infection, these cells accumulate in the marginal zone region. Recruitment of infected CD11c(+)Gr-1(+) cells to the spleen is partially dependent upon signaling through chemokine receptor CCR2. Intracellular cytokine staining demonstrates that infected, but not noninfected, splenic CD11c(+)Gr-1(+) dendritic cells are suppressed in their ability to respond to ex vivo TLR stimulation. We hypothesize that Toxoplasma exploits pDCs as Trojan horses, targeting them for early infection, suppressing their cytokine effector function, and using them for dissemination within the host.
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            Cytokine regulation of immunopathology in toxoplasmosis.

            Pamela J Gaddi, George Yap (2015)
            Toxoplasma gondii infection is an important cause of central nervous system and ocular disease, both in immunocompromised and in certain immunocompetent populations. Although parasite-mediated host cell lysis is probably the principal cause of tissue destruction in immunodeficiency states, hypersensitivity and inflammatory responses may underlie severe disease in otherwise immuno-sufficient individuals. In this review, we have critically evaluated the body of experimental evidence indicating a role of CD4 T cells in systemic and local immunopathology associated with T. gondii infection. We also discuss the pathogenic roles of cytokines produced by T helper (Th) 1 and Th17 cells and the protective and homeostatic roles of interleukin (IL)-10, transforming growth factor-beta and IL-27 in modulating hypersensitivity responses induced by T. gondii.
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              Regulation of the expression of nitric oxide synthase and leishmanicidal activity by glycoconjugates of Leishmania lipophosphoglycan in murine macrophages.

              Wenbin Wei, Heather M Ferguson, L Proudfoot … (1996)
              Lipophosphoglycan (LPG) glycoconjugates from promastigotes of Leishmania were not able to induce the expression of the cytokine-inducible nitric oxide synthase (iNOS) by the murine macrophage cell line, J774. However, they synergize with interferon gamma to stimulate the macrophages to express high levels of iNOS. This synergistic effect was critically time-dependent. Preincubation of J774 cells with the LPG glycans 4-18 h before stimulation with interferon gamma resulted in a significant reduction in the expression of iNOS mRNA and of NO synthesis, compared with cells preincubated with culture medium alone. The regulatory effect on the induction of iNOS by LPG is located in the LPG phosphoglycan disaccharide backbone. Synthetic fragments of this backbone had a similar regulatory effect on NO synthesis. Further, the production of NO by activated macrophages in the present system was correlated directly with the leishmanicidal capacity of the cells. These data therefore demonstrate that LPG glycoconjugates have a profound effect on the survival of Leishmania parasites through their ability to regulate the expression of iNOS by macrophages.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Korean J Parasitol
                Journal ID (iso-abbrev): Korean J. Parasitol
                Title: The Korean Journal of Parasitology
                Publisher: The Korean Society for Parasitology and Tropical Medicine
                ISSN (Print): 0023-4001
                ISSN (Electronic): 1738-0006
                Publication date (Print): April 2019
                Publication date (Electronic): 30 April 2019
                Volume: 57
                Issue: 2
                Pages: 201-206
                Affiliations
                [1 ]Department of Environmental Medical Biology and Institute of Tropical Medicine, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea
                [2 ]Department of Environmental Biology and Medical Parasitology, Hanyang University College of Medicine, Seoul 04763, Korea
                Author notes
                [* ]Corresponding author ( mhahn@ 123456hanyang.ac.kr )
                Article
                Publisher ID: kjp-57-2-201
                DOI: 10.3347/kjp.2019.57.2.201
                PMC ID: 6526212
                PubMed ID: 31104415
                SO-VID: dc1c922e-2f51-40a0-8856-5283367b66fa
                Copyright © Copyright © 2019 by The Korean Society for Parasitology and Tropical Medicine
                License:

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

                History
                Date received : 10 December 2018
                Date revision received : 14 March 2019
                Date accepted : 19 March 2019
                Categories
                Subject: Brief Communication

                ScienceOpen disciplines: Parasitology
                Keywords: toxoplasma gondii,mast cell,cytokine,nitric oxide
                Data availability:
                ScienceOpen disciplines: Parasitology
                Keywords: toxoplasma gondii, mast cell, cytokine, nitric oxide

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