PD-1 AND TIM-3 EXPRESSION ON DIFFERENT SUBPOPULATIONS OF MONOCYTES IN CHRONIC OFTEN RECURRENT HERPESVIRUS INFECTION
- Authors: Rashchupkin I.M.1, Meledina I.V.1, Kotova M.A.1, Zheltova O.I.1
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Affiliations:
- Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation
- Section: Joint Immunology Forum 2024
- URL: https://rusimmun.ru/jour/article/view/16807
- DOI: https://doi.org/10.46235/1028-7221-16807-PAT
- ID: 16807
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Abstract
More than half of the world's population is infected with the herpes simplex virus. In most cases, infection is not accompanied by symptoms, but in some people the disease occurs as a chronic infection with frequent and severe relapses. One of the most likely reasons for this may be a dysregulation of the immune system. In recent years, the role of checkpoint molecules, in particular PD-1 and Tim-3, in the regulation of the immune response and the functions of immunocompetent cells has been actively studied. Activation of PD-1 and Tim-3 on T cells has previously been shown to suppress the immune response. PD-1 and Tim-3 are also expressed on other immune cells, in particular monocytes. However, the expression of these molecules on monocytes during chronic viral infections has not been previously studied. The study was aimed at assessing the level of PD-1 and Tim-3 expression on various populations of monocytes in patients with chronic often recurrent herpesvirus infection. 26 patients were recruited into the study. All patients received antiviral and immunomodulatory therapy in the immunological department. The number of classical, intermediate, and non-classical monocytes and the expression of PD-1 and Tim-3 on monocytes, were assessed by flow cytometry before and after the therapy. Monocytes were isolated from peripheral blood, and subpopulations were divided according to the level of expression of CD14 and CD16. In patients with herpes, a reduced number of monocytes was observed in comparison with healthy donors. The relative number of PD-1-positive monocytes, the mean fluorescence intensity of PD-1 and Tim-3, and the number of double-positive cells were reduced in herpes patients in all three monocyte subpopulations examined. 3 months after the therapy, the response to the therapy was assessed; patients who did not have a single recurrence of herpes within 3 months were considered to respond. Responding patients had a lower initial content of double-positive cells among intermediate and non-classical monocytes. The decrease in the level of PD-1 and Tim-3 positive monocytes during herpesvirus infection revealed in the present study may indicate the involvement of monocytes deficient in the expression of checkpoint molecules in the pathogenesis of the disease.
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About the authors
Ivan Mikhailovich Rashchupkin
Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation
Email: iwwwanbets@mail.ru
ORCID iD: 0009-0007-3528-3783
assistant researcher, Laboratory of Cellular Immunotherapy
Russian Federation, 630099, Novosibirsk, ul. Yadrintsevskaya, 14Ilona Valerevna Meledina
Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation
Email: ct_lab@mail.ru
Candidate of Science in Medicine, allergist-immunologist, Head, Immunology Department, Clinic of Immunopathology
Russian Federation, Novosibirsk, ul. Yadrintsevskaya, 14Mariya Andreevna Kotova
Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation
Email: ct_lab@mail.ru
allergist-immunologist, Immunology Department, Clinic of Immunopathology
Russian Federation, 630099, Novosibirsk, ul. Yadrintsevskaya, 14Olga Igorevna Zheltova
Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation
Author for correspondence.
Email: ct_lab@mail.ru
Candidate of Science in Medicine, allergist-immunologist, Immunology Department, Clinic of Immunopathology
Russian Federation, 630099, Novosibirsk, ul. Yadrintsevskaya, 14References
- Antonsen K.W., Hviid C.V.B., Hagensen M.K., Sorensen B.S., Moller H.J. Soluble PD-1 (sPD-1) is expressed in human macrophages. Cellular Immunology, 2021, Vol. 369: 104435. doi: 10.1016/j.cellimm.2021.104435
- Bellner L., Thoren F., Nygren E., Liljeqvist J-A., Karlsson A., Eriksson K. A proinflammatory peptide from herpes simplex virus type 2 glycoprotein G affects neutrophil, monocyte, and NK cell functions. Journal of Immunology, 2005, Vol. 174, no.4, pp. 2235-2241. doi: 10.4049/jimmunol.174.4.2235
- Das M., Zhu C., Kuchroo V.K. Tim-3 and its role in regulating anti-tumor immunity. Immunological Reviews, 2017, Vol. 276, no.1, pp. 97-111. doi: 10.1111/imr.12520
- Ghosh C., Luong G., Sun Y. A snapshot of the PD-1/PD-L1 pathway. Journal of Cancer, 2021, Vol. 12, no.9, pp. 2735-2746. doi: 10.7150/jca.57334
- Guglietta S, Krieg C. Phenotypic and functional heterogeneity of monocytes in health and cancer in the era of high dimensional technologies. Blood Reviews, 2023, Vol. 58: 101012. doi: 10.1016/j.blre.2022.101012.
- Guignant C., Lepape A., Huang X., Kherouf H., Denis L., Poitevin F., Malcus C., Cheron A., Allaouchiche B., Gueyffier F., Ayala A., Monneret G., Venet F. Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients. Critical Care, 2011, Vol. 15, no.2. doi: 10.1186/cc10112
- Ozanska A., Szumczak D., Rybka J. Pattern of human monocyte subpopulations in health and disease. Scandinavian Journal of Immunology, 2020, Vol. 91, no.1, e12883. doi: 10.1111/sji.12883.
- Skrzeczynska-Moncznik J., Bzowska M., Loseke S., Grage-Griebenow E., Zembala M., Pryjma J. Peripheral blood CD14high CD16+ monocytes are main producers of IL-10. Scandinavian Journal of Immunology, 2011, Vol. 67, no.2, pp. 152-159. doi: 10.1111/j.1365-3083.2007.02051.x.
- Van Wagoner N., Qushair F., Johnston C. Genital herpes infection: progress and problems. Infectious Disease Clinics of North America, 2023, Vol. 37, no.2, pp. 351-367. doi: 10.1016/j.idc.2023.02.011
- Xia Q., Wei L., Zhang Y., Sheng J., Wu W., Zhang Y. Immune Checkpoint Receptors Tim-3 and PD-1 Regulate Monocyte and T Lymphocyte Function in Septic Patients. Mediators of inflammation, 2018, Vol. 2018: 1632902. doi: 10.1155/2018/1632902
- Zhu S., Viejo-Borbolla A. Pathogenesis and virulence of herpes simplex virus. Virulence, 2021, Vol. 12, no.1, pp. 2670-2702. doi: 10.1080/21505594.2021.1982373