Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells

The search for and analysis of new ligands for innate immunity receptors are of special significance for understanding the regulatory mechanisms of immune response. Here we show that the major heat shock protein 70 (Hsp70) can bind to and activate TREM-1, the innate immunity receptor expressed on mo...

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Main Authors: Tatiana N. Sharapova, Elena A. Romanova, Olga K. Ivanova, Denis V. Yashin, Lidia P. Sashchenko
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:International Journal of Molecular Sciences
Subjects:
NK
Online Access:https://www.mdpi.com/1422-0067/22/13/6889
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spelling doaj-797578f5e14644559bdbb64de0f301c62021-07-15T15:37:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-01226889688910.3390/ijms22136889Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor CellsTatiana N. Sharapova0Elena A. Romanova1Olga K. Ivanova2Denis V. Yashin3Lidia P. Sashchenko4Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, Vavilova 34/5, 111394 Moscow, RussiaLaboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, Vavilova 34/5, 111394 Moscow, RussiaLaboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, Vavilova 34/5, 111394 Moscow, RussiaLaboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, Vavilova 34/5, 111394 Moscow, RussiaLaboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, Vavilova 34/5, 111394 Moscow, RussiaThe search for and analysis of new ligands for innate immunity receptors are of special significance for understanding the regulatory mechanisms of immune response. Here we show that the major heat shock protein 70 (Hsp70) can bind to and activate TREM-1, the innate immunity receptor expressed on monocytes. The Hsp70–TREM-1 interaction activates expression of TNFα and IFNγ mRNAs in monocytes and stimulates IL-2 secretion by PBMCs. Moreover, incubation of PBMCs with Hsp70 leads to an appearance of cytotoxic lymphocyte subpopulations active against the MHC-negative tumor cells. In addition, both the CD4+ T-lymphocytes and CD14+ monocytes are necessary for the Hsp70 signal transduction and a consequent activation of the cytotoxic lymphocytes. We believe that data presented in this study will broaden the views on the involvement of Hsp70 in the antitumor immunity.https://www.mdpi.com/1422-0067/22/13/6889monocytesHsp70NKcytotoxicitycytokine
collection DOAJ
language English
format Article
sources DOAJ
author Tatiana N. Sharapova
Elena A. Romanova
Olga K. Ivanova
Denis V. Yashin
Lidia P. Sashchenko
spellingShingle Tatiana N. Sharapova
Elena A. Romanova
Olga K. Ivanova
Denis V. Yashin
Lidia P. Sashchenko
Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells
International Journal of Molecular Sciences
monocytes
Hsp70
NK
cytotoxicity
cytokine
author_facet Tatiana N. Sharapova
Elena A. Romanova
Olga K. Ivanova
Denis V. Yashin
Lidia P. Sashchenko
author_sort Tatiana N. Sharapova
title Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells
title_short Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells
title_full Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells
title_fullStr Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells
title_full_unstemmed Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells
title_sort hsp70 interacts with the trem-1 receptor expressed on monocytes and thereby stimulates generation of cytotoxic lymphocytes active against mhc-negative tumor cells
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2021-06-01
description The search for and analysis of new ligands for innate immunity receptors are of special significance for understanding the regulatory mechanisms of immune response. Here we show that the major heat shock protein 70 (Hsp70) can bind to and activate TREM-1, the innate immunity receptor expressed on monocytes. The Hsp70–TREM-1 interaction activates expression of TNFα and IFNγ mRNAs in monocytes and stimulates IL-2 secretion by PBMCs. Moreover, incubation of PBMCs with Hsp70 leads to an appearance of cytotoxic lymphocyte subpopulations active against the MHC-negative tumor cells. In addition, both the CD4+ T-lymphocytes and CD14+ monocytes are necessary for the Hsp70 signal transduction and a consequent activation of the cytotoxic lymphocytes. We believe that data presented in this study will broaden the views on the involvement of Hsp70 in the antitumor immunity.
topic monocytes
Hsp70
NK
cytotoxicity
cytokine
url https://www.mdpi.com/1422-0067/22/13/6889
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