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A critical Blimp-1-dependent IL-10 regulatory pathway in T cells protects from a lethal pro-inflammatory cytokine storm during acute experimental Trypanosoma brucei Infection

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Abstract
In many infectious diseases, the immune response operates as a double-edged sword. While required for protective immunity, infection-induced inflammation can be detrimental if it is not properly controlled, causing collateral body damage and potentially leading to death. It is in this context that the potent anti-inflammatory cytokine interleukin-10 (IL-10) is required to dampen the pro-inflammatory immune response that hallmarks trypanosomosis. Effective control of this infection requires not just the action of antibodies specific for the parasite's variable surface glycoprotein (VSG) coat antigens, but also a pro-inflammatory immune response mediated mainly by IFN gamma, TNF, and NO. However, strict control of inflammation is mandatory, as IL-10-deficient mice succumb from an unrestrained cytokine storm within 10 days of aTrypanosome bruceiinfection. The relevant cellular source of IL-10 and the associated molecular mechanisms implicated in its trypanosomosis associated production are poorly understood. Using an IL-10 reporter mouse strain (Vert-X), we demonstrate here that NK cells, CD8(+)T cells and CD4(+)T cells as well as B cells and plasma cells constitute potential cellular sources of IL-10 within the spleen and liver during acute infection. The IL-10 wave follows peak pro-inflammatory cytokine production, which accompanied the control of peak parasitemia. Similar results were observed following conventional experimental needle infection and physiological infections viaT. brucei-infected tsetse flies. Our results show that conditional T cell-specific ablation of the IL-10 regulatingPrdm1gene (encoding for the Blimp-1 transcription factor), leads to an uncontrolled trypanosome-induced pro-inflammatory syndrome like the one observed in infected IL-10-deficient mice. This result indicates that the biological role of IL-10-derived from non-T cells, including NK cells, is of minor importance when considering host survival. The cytokine IL-27 that is also considered to be an IL-10 regulator, did not affect IL-10 production during infection. Together, these data suggest thatT. bruceiactivates a Blimp-1-dependent IL-10 regulatory pathway in T cells that acts as a critical anti-inflammatory rheostat, mandatory for host survival during the acute phase of parasitemia.
Keywords
T, brucei, IL-10, inflammation, T cells, IL-27, Blimp-1, TRANSCRIPTIONAL REPRESSOR BLIMP-1, IFN-GAMMA, B-CELLS, AFRICAN TRYPANOSOMIASIS, INTERFERON-GAMMA, EXPRESSION, INFECTION, MICE, INTERLEUKIN-27, RESISTANCE

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MLA
De Trez, Carl, et al. “A Critical Blimp-1-Dependent IL-10 Regulatory Pathway in T Cells Protects from a Lethal pro-Inflammatory Cytokine Storm during Acute Experimental Trypanosoma Brucei Infection.” FRONTIERS IN IMMUNOLOGY, vol. 11, 2020, doi:10.3389/fimmu.2020.01085.
APA
De Trez, C., Stijlemans, B., Bockstal, V., Cnops, J., Korf, H., Van Snick, J., … Magez, S. (2020). A critical Blimp-1-dependent IL-10 regulatory pathway in T cells protects from a lethal pro-inflammatory cytokine storm during acute experimental Trypanosoma brucei Infection. FRONTIERS IN IMMUNOLOGY, 11. https://doi.org/10.3389/fimmu.2020.01085
Chicago author-date
De Trez, Carl, Benoit Stijlemans, Viki Bockstal, Jennifer Cnops, Hannelie Korf, Jacques Van Snick, Guy Caljon, et al. 2020. “A Critical Blimp-1-Dependent IL-10 Regulatory Pathway in T Cells Protects from a Lethal pro-Inflammatory Cytokine Storm during Acute Experimental Trypanosoma Brucei Infection.” FRONTIERS IN IMMUNOLOGY 11. https://doi.org/10.3389/fimmu.2020.01085.
Chicago author-date (all authors)
De Trez, Carl, Benoit Stijlemans, Viki Bockstal, Jennifer Cnops, Hannelie Korf, Jacques Van Snick, Guy Caljon, Eric Muraille, Ian R. Humphreys, Louis Boon, Jo A. Van Ginderachter, and Stefan Magez. 2020. “A Critical Blimp-1-Dependent IL-10 Regulatory Pathway in T Cells Protects from a Lethal pro-Inflammatory Cytokine Storm during Acute Experimental Trypanosoma Brucei Infection.” FRONTIERS IN IMMUNOLOGY 11. doi:10.3389/fimmu.2020.01085.
Vancouver
1.
De Trez C, Stijlemans B, Bockstal V, Cnops J, Korf H, Van Snick J, et al. A critical Blimp-1-dependent IL-10 regulatory pathway in T cells protects from a lethal pro-inflammatory cytokine storm during acute experimental Trypanosoma brucei Infection. FRONTIERS IN IMMUNOLOGY. 2020;11.
IEEE
[1]
C. De Trez et al., “A critical Blimp-1-dependent IL-10 regulatory pathway in T cells protects from a lethal pro-inflammatory cytokine storm during acute experimental Trypanosoma brucei Infection,” FRONTIERS IN IMMUNOLOGY, vol. 11, 2020.
@article{8671133,
  abstract     = {{In many infectious diseases, the immune response operates as a double-edged sword. While required for protective immunity, infection-induced inflammation can be detrimental if it is not properly controlled, causing collateral body damage and potentially leading to death. It is in this context that the potent anti-inflammatory cytokine interleukin-10 (IL-10) is required to dampen the pro-inflammatory immune response that hallmarks trypanosomosis. Effective control of this infection requires not just the action of antibodies specific for the parasite's variable surface glycoprotein (VSG) coat antigens, but also a pro-inflammatory immune response mediated mainly by IFN gamma, TNF, and NO. However, strict control of inflammation is mandatory, as IL-10-deficient mice succumb from an unrestrained cytokine storm within 10 days of aTrypanosome bruceiinfection. The relevant cellular source of IL-10 and the associated molecular mechanisms implicated in its trypanosomosis associated production are poorly understood. Using an IL-10 reporter mouse strain (Vert-X), we demonstrate here that NK cells, CD8(+)T cells and CD4(+)T cells as well as B cells and plasma cells constitute potential cellular sources of IL-10 within the spleen and liver during acute infection. The IL-10 wave follows peak pro-inflammatory cytokine production, which accompanied the control of peak parasitemia. Similar results were observed following conventional experimental needle infection and physiological infections viaT. brucei-infected tsetse flies. Our results show that conditional T cell-specific ablation of the IL-10 regulatingPrdm1gene (encoding for the Blimp-1 transcription factor), leads to an uncontrolled trypanosome-induced pro-inflammatory syndrome like the one observed in infected IL-10-deficient mice. This result indicates that the biological role of IL-10-derived from non-T cells, including NK cells, is of minor importance when considering host survival. The cytokine IL-27 that is also considered to be an IL-10 regulator, did not affect IL-10 production during infection. Together, these data suggest thatT. bruceiactivates a Blimp-1-dependent IL-10 regulatory pathway in T cells that acts as a critical anti-inflammatory rheostat, mandatory for host survival during the acute phase of parasitemia.}},
  articleno    = {{1085}},
  author       = {{De Trez, Carl and Stijlemans, Benoit and Bockstal, Viki and Cnops, Jennifer and Korf, Hannelie and Van Snick, Jacques and Caljon, Guy and Muraille, Eric and Humphreys, Ian R. and Boon, Louis and Van Ginderachter, Jo A. and Magez, Stefan}},
  issn         = {{1664-3224}},
  journal      = {{FRONTIERS IN IMMUNOLOGY}},
  keywords     = {{T,brucei,IL-10,inflammation,T cells,IL-27,Blimp-1,TRANSCRIPTIONAL REPRESSOR BLIMP-1,IFN-GAMMA,B-CELLS,AFRICAN TRYPANOSOMIASIS,INTERFERON-GAMMA,EXPRESSION,INFECTION,MICE,INTERLEUKIN-27,RESISTANCE}},
  language     = {{eng}},
  pages        = {{15}},
  title        = {{A critical Blimp-1-dependent IL-10 regulatory pathway in T cells protects from a lethal pro-inflammatory cytokine storm during acute experimental Trypanosoma brucei Infection}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2020.01085}},
  volume       = {{11}},
  year         = {{2020}},
}

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