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Sci Rep. 2017 Sep 6;7(1):10740. doi: 10.1038/s41598-017-11354-2.

The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant.

Author information

1
CIC bioGUNE, 48160, Derio, Bizkaia, Spain.
2
Ikerbasque, Basque Foundation for Science, 48013, Bilbao, Bizkaia, Spain.
3
Department of Animal Medicine and Surgery, School of Veterinary Medicine, Complutense University of Madrid, 28040, Madrid, Spain.
4
Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Instituto de Salud Carlos III, 28029, Madrid, Spain.
5
Centro de Investigación Biomédica en Red en cáncer (CIBERonc), Instituto de Salud Carlos III, 28029, Madrid, Spain.
6
Department of Biochemistry and Molecular Biology, University of the Basque Country, 48940, Leioa, Bizkaia, Spain.
7
Molecular Nutrition and Metabolism, Institute of Food Science Research (CIAL, CSIC), 28049, Madrid, Spain.
8
CIC bioGUNE, 48160, Derio, Bizkaia, Spain. janguita@cicbiogune.es.
9
Ikerbasque, Basque Foundation for Science, 48013, Bilbao, Bizkaia, Spain. janguita@cicbiogune.es.

Abstract

Salp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in the inhibition of early signaling events and the production of the autocrine growth factor, interleukin-2. The fate of the CD4 T cells activated in the presence of Salp15 or its long-term effects are, however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished cross-antigenic antibody production even after interruption of the treatment with the protein. Transcriptionally, the salivary protein provokes an acute effect that includes known activation markers, such as Il2 or Cd44, and that fades over time. The long-term effects exerted by Salp15 do not involve the induction of either anergy traits nor increased populations of regulatory T cells. Similarly, the treatment with Salp15 does not result in B cell anergy or the generation of myeloid suppressor cells. However, Salp15 induces the increased expression of the ectoenzyme, CD73, in regulatory T cells and increased production of adenosine. Our study provides a profound characterization of the immunomodulatory activity of Salp15 and suggests that its long-term effects are due to the specific regulation of CD73.

PMID:
28878331
PMCID:
PMC5587732
DOI:
10.1038/s41598-017-11354-2
[Indexed for MEDLINE]
Free PMC Article

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