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The Ly49E receptor inhibits the immune control of acute Trypanosoma cruzi infection

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Abstract
The protozoan parasite Trypanosoma cruzi circulates in the blood upon infection and invades various cells. Parasites intensively multiply during the acute phase of infection and persist lifelong at low levels in tissues and blood during the chronic phase. Natural killer (NK) and NKT cells play an important role in the immune control of T. cruzi infection, mainly by releasing the cytokine IFN-gamma that activates the microbicidal action of macrophages and other cells and shapes a protective type 1 immune response. The mechanisms by which immune cells are regulated to produce IFN-gamma during T. cruzi infection are still incompletely understood. Here, we show that urokinase plasminogen activator (uPA) is induced early upon T. cruzi infection and remains elevated until day 20 post-infection. We previously demonstrated that the inhibitory receptor Ly49E, which is expressed, among others, on NK and NKT cells, is triggered by uPA. Therefore, we compared wild type (WT) to Ly49E knockout (KO) mice for their control of experimental T. cruzi infection. Our results show that young, i.e., 4- and 6-week-old, Ly49E KO mice control the infection better than WT mice, indicated by a lower parasite load and less cachexia. The beneficial effect of Ly49E depletion is more obvious in 4- week-old male than in female mice and weakens in 8-week-old mice. In young mice, the lower T. cruzi parasitemia in Ly49E KO mice is paralleled by higher IFN-gamma production compared to their WT controls. Our data indicate that Ly49E receptor expression inhibits the immune control of T. cruzi infection. This is the first demonstration that the inhibitory Ly49E receptor can interfere with the immune response to a pathogen in vivo.
Keywords
NATURAL-KILLER-CELLS, IFN-GAMMA PRODUCTION, NK CELLS, T-CELLS, PLASMINOGEN-ACTIVATOR, CHAGAS-DISEASE, EARLY-LIFE, DELTA-T, EXPRESSION, MICE, Ly49E receptor, natural killer cells, Trypanosoma cruzi, immune control, urokinase plasminogen activator, IFN-gamma

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Chicago
Filtjens, Jessica, Nicolas Coltel, Sabrina Cencig, Sylvie Taveirne, Els Van Ammel, Aline Van Acker, Tessa Kerre, et al. 2016. “The Ly49E Receptor Inhibits the Immune Control of Acute Trypanosoma Cruzi Infection.” Frontiers in Immunology 7.
APA
Filtjens, J., Coltel, N., Cencig, S., Taveirne, S., Van Ammel, E., Van Acker, A., Kerre, T., et al. (2016). The Ly49E receptor inhibits the immune control of acute Trypanosoma cruzi infection. FRONTIERS IN IMMUNOLOGY, 7.
Vancouver
1.
Filtjens J, Coltel N, Cencig S, Taveirne S, Van Ammel E, Van Acker A, et al. The Ly49E receptor inhibits the immune control of acute Trypanosoma cruzi infection. FRONTIERS IN IMMUNOLOGY. 2016;7.
MLA
Filtjens, Jessica, Nicolas Coltel, Sabrina Cencig, et al. “The Ly49E Receptor Inhibits the Immune Control of Acute Trypanosoma Cruzi Infection.” FRONTIERS IN IMMUNOLOGY 7 (2016): n. pag. Print.
@article{8509449,
  abstract     = {The protozoan parasite Trypanosoma cruzi circulates in the blood upon infection and invades various cells. Parasites intensively multiply during the acute phase of infection and persist lifelong at low levels in tissues and blood during the chronic phase. Natural killer (NK) and NKT cells play an important role in the immune control of T. cruzi infection, mainly by releasing the cytokine IFN-gamma that activates the microbicidal action of macrophages and other cells and shapes a protective type 1 immune response. The mechanisms by which immune cells are regulated to produce IFN-gamma during T. cruzi infection are still incompletely understood. Here, we show that urokinase plasminogen activator (uPA) is induced early upon T. cruzi infection and remains elevated until day 20 post-infection. We previously demonstrated that the inhibitory receptor Ly49E, which is expressed, among others, on NK and NKT cells, is triggered by uPA. Therefore, we compared wild type (WT) to Ly49E knockout (KO) mice for their control of experimental T. cruzi infection. Our results show that young, i.e., 4- and 6-week-old, Ly49E KO mice control the infection better than WT mice, indicated by a lower parasite load and less cachexia. The beneficial effect of Ly49E depletion is more obvious in 4- week-old male than in female mice and weakens in 8-week-old mice. In young mice, the lower T. cruzi parasitemia in Ly49E KO mice is paralleled by higher IFN-gamma production compared to their WT controls. Our data indicate that Ly49E receptor expression inhibits the immune control of T. cruzi infection. This is the first demonstration that the inhibitory Ly49E receptor can interfere with the immune response to a pathogen in vivo.},
  articleno    = {472},
  author       = {Filtjens, Jessica and Coltel, Nicolas and Cencig, Sabrina and Taveirne, Sylvie and Van Ammel, Els and Van Acker, Aline and Kerre, Tessa and Matthys, Patrick and Taghon, Tom and Vandekerckhove, Bart and Carlier, Yves and Truyens, Carine and Leclercq, Georges},
  issn         = {1664-3224},
  journal      = {FRONTIERS IN IMMUNOLOGY},
  keyword      = {NATURAL-KILLER-CELLS,IFN-GAMMA PRODUCTION,NK CELLS,T-CELLS,PLASMINOGEN-ACTIVATOR,CHAGAS-DISEASE,EARLY-LIFE,DELTA-T,EXPRESSION,MICE,Ly49E receptor,natural killer cells,Trypanosoma cruzi,immune control,urokinase plasminogen activator,IFN-gamma},
  language     = {eng},
  pages        = {11},
  title        = {The Ly49E receptor inhibits the immune control of acute Trypanosoma cruzi infection},
  url          = {http://dx.doi.org/10.3389/fimmu.2016.00472},
  volume       = {7},
  year         = {2016},
}

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