AN IMPACT OF LATENT TOXOPLASMOSIS REACTIVATION ON IMMUNE SYSTEM AND CLINICAL DYNAMICS IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT



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Abstract

Mild cognitive impairment (MCI) in a number of cases precedes the development of dementia. Neuroinflammation is one of the key factors in neurodegeneration pathogenesis. Chronic infections and parasitic infestations contribute significantly to neuroinflammation. It has been evident about a link between systemic inflammation, disorders of cellular and humoral immunity and MCI progression. In this context, of particular interest is a role for a common intracellular pathogen Toxoplasma gondii may be involved in MCI pathogenesis and clinical dynamics. Currently, the frequency and clinical significance of toxoplasmosis reactivation in MCI remain unknown. Given Toxoplasma gondii-related immunotropic effects, it is also relevant to investigate an association between latent toxoplasmosis reactivation, immune parameters and inflammatory mediators in MCI. The study was aimed at assessing the frequency of chronic toxoplasmosis reactivation and its associations with cell immunity, levels of main cytokines and chemokines along with clinical dynamics in MCI. For this, individuals were divided into the following groups: main group included 130 patients with MCI, and comparison group – 81 patients with subjective cognitive impairment (preMCI). The serum was tested for anti-Toxoplasma gondii IgG, IgM, and IgA antibodies using enzyme-linked immunosorbent assay, the concentration of cytokines and chemokines was determined by multiplex assay. Cell immunity was assessed using flow cytometry. The Kruskal-Wallis test was used to assess the significance of differences, followed by pairwise comparisons with Mann-Whitney test. An increased frequency of latent toxoplasmosis reactivation (positive for anti-Toxoplasma gondii IgA in combination with IgG >50 IU/mL) was observed in MCI. In MCI patients, reactivation of toxoplasmosis was associated with impaired activation of Th1-cell immunity (lower total and subset T-cell counts including CD4+CD57+ T-cells and CD8+CD57+ T-cells), as well as increased levels and activation of NK-cells. Higher anti-Toxoplasma gondii IgG level in patients was associated with elevated neuroinflammatory markers CCL4 and CCL20, and with less favorable one-year-follow-up clinical dynamics. The results suggest that reactivation of latent toxoplasmosis in MCI may be clinically relevant, and it is important to determine not only anti-Toxoplasma gondii IgG and IgM, but also IgA to detect it.

About the authors

Irina K. Malashenkova

National Research Center “Kurchatov Institute”, Moscow, Russia;
Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia;
N. Alekseev Psychiatric Clinical Hospital No. 1, Moscow, Russia

Email: malashenkova.irina@bk.ru
ORCID iD: 0000-0002-3604-9098
SPIN-code: 4205-6010
Scopus Author ID: 6508276299
ResearcherId: HSC-4066-2023

PhD (Medicine), Principal researcher, Laboratory of Cell Biology, Molecular Medicine and Immunology, National Research Center “Kurchatov Institute”; Senior researcher, Laboratory of Clinical Immunology, Federal Research and Clinical Center of Physical-Chemical Medicine; Senior researcher, Department of Epidemiology and Prophylaxis of Mental Disorders, N. Alekseev Psychiatric Clinical Hospital No. 1

Россия, 123182, Russia, akademika Kurchatova sq., 1; 119435, Russia, Malaya Pirogovskaya st., 1A; 117152, Russia, Zagorodnoye shosse, 2.

Sergey Krynskiy

National Research Center “Kurchatov Institute”, Moscow, Russia;
N. Alekseev Psychiatric Clinical Hospital No. 1, Moscow, Russia

Email: srgkr002@gmail.com
ORCID iD: 0000-0003-4328-865X
SPIN-code: 4465-0413
Scopus Author ID: 55965386600
ResearcherId: AAE-3103-2020

PhD (Medicine), Senior researcher, Laboratory of Cell Biology, Molecular Medicine and Immunology, National Research Center “Kurchatov Institute”; Junior researcher, Department of Mental Disorders in Neurodegenerative Diseases of the brain, N. Alekseev Psychiatric Clinical Hospital No. 1

Россия, 123182, Russia, akademika Kurchatova sq., 1; 117152, Russia, Zagorodnoye shosse, 2

Nikita A. Khailov

National Research Center “Kurchatov Institute”, Moscow, Russia

Email: nik_khailov@bk.ru
ORCID iD: 0000-0002-3693-285X
SPIN-code: 7926-9505
Scopus Author ID: 7801569112

PhD (Medicine), Senior researcher, Resource Center for Molecular and Cellular Biology

Россия, 123182, Russia, akademika Kurchatova sq., 1

Andrey Y. Ratushnyy

Russian State Research Center “Institute of Biomedical Problems”, Moscow, Russia

Email: Ratushkin@mail.ru
ORCID iD: 0000-0002-3913-6584
SPIN-code: 7200-8919
Scopus Author ID: 57193279274
ResearcherId: R-2740-2017

PhD (Biology), Researcher

Россия, 123007, Russia, Khoroshevskoe Shosse, 76A

Daniil P. Ogurtsov

National Research Center “Kurchatov Institute”, Moscow, Russia;
Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia

Email: ogurtsovdp@gmail.com
ORCID iD: 0000-0003-0257-4713
SPIN-code: 7288-1161
Scopus Author ID: 57188826245
ResearcherId: AAE-5647-2020

PhD (Medicine), Senior researcher, Laboratory of Cell Biology, Molecular Medicine and Immunology, National Research Center “Kurchatov Institute”; Researcher, Laboratory of Clinical Immunology, Federal Research and Clinical Center of Physical-Chemical Medicine

Россия, 123182, Russia, akademika Kurchatova sq., 1; Moscow, 119435, Russia, Malaya Pirogovskaya st., 1A

Ksenia A. Chernyakova

National Research Center “Kurchatov Institute”, Moscow, Russia

Email: ksyu2018.03@mail.ru

Research technician, Laboratory of Cell Biology, Molecular Medicine and Immunology

Россия, 123182, Russia, akademika Kurchatova sq., 1

Olesya V. Anufrieva

National Research Center “Kurchatov Institute”, Moscow, Russia;
State federal-funded educational institution of higher professional training I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia

Email: benrimasalmin@bk.ru

Research technician, Laboratory of Cell Biology, Molecular Medicine and Immunology, National Research Center “Kurchatov Institute”; Student, State federal-funded educational institution of higher professional training I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation

Россия, 123182, Russia, akademika Kurchatova sq., 1; 119048, Russia, Trubetskaya st., 8, 2

Dmitry B. Goncharov

N.F. Gamaleya Federal Research Center for Epidemiology and Microbiology, Ministry of Health of Russia, Moscow, Russia

Email: goncharov_toxo@mail.ru
ORCID iD: 0000-0002-0250-4902
SPIN-code: 2486-2330
Scopus Author ID: 6603939710

PhD (Biology), Head of Laboratory of Protozoal Infections

Россия, 123098, Russia, Gamaleya st., 18

Evgeniya V. Abbazova

N.F. Gamaleya Federal Research Center for Epidemiology and Microbiology, Ministry of Health of Russia, Moscow, Russia

Email: janifer@inbox.ru
ORCID iD: 0000-0001-6328-8142
SPIN-code: 2953-9764
Scopus Author ID: 57947383200

PhD (Medicine), Researcher, Laboratory of Protozoal Infections

Россия, 123098, Russia, Gamaleya st., 18

Marina S. Baranets

N.F. Gamaleya Federal Research Center for Epidemiology and Microbiology, Ministry of Health of Russia, Moscow, Russia

Email: shizotorex@mail.ru
ORCID iD: 0000-0002-3466-3588
SPIN-code: 1222-0286
Scopus Author ID: 49961088000
ResearcherId: U-4961-2017

PhD (Medicine), Senior researcher, Laboratory of Protozoal Infections

Россия, 123098, Russia, Gamaleya st., 18

Alisa V. Andryushchenko

N. Alekseev Psychiatric Clinical Hospital No. 1, Moscow, Russia;
Lomonosov Moscow State University, Moscow, Russia

Email: alissia.va@mail.ru
ORCID iD: 0000-0002-7702-6343
SPIN-code: 8864-3341
Scopus Author ID: 7003779950
ResearcherId: ABH-7755-2020

PhD, Doctor of Science (Medicine), Associate Professor; Professor of the Department of Mental Health of Lomonosov Moscow State University, Faculty of Psychology; Head of the Department of Mental Disorders in Neurodegenerative Diseases of the brain, N. Alekseev Psychiatric Clinical Hospital No. 1

Россия, 117152, Russia, Zagorodnoye shosse, 2; Russia, 125009, Mokhovaya st., 11, 9

Victor B. Savilov

N. Alekseev Psychiatric Clinical Hospital No. 1, Moscow, Russia

Email: vsavilov@mail.ru
SPIN-code: 9025-0496

Head of the Medical rehabilitation department "Memory Clinic", N. Alekseev Psychiatric Clinical Hospital No. 1

Россия, Russia, 117152, Zagorodnoye shosse, 2

Georgy P. Kostyuk

N. Alekseev Psychiatric Clinical Hospital No. 1, Moscow, Russia

Email: kgr@yandex.ru
ORCID iD: 0000-0003-4320-3644
SPIN-code: 3424-4544
Scopus Author ID: 57200081884
ResearcherId: AAA-1682-2020

PhD, MD, Doctor of Science (Medicine), Professor; Chief physician, N. Alekseev Psychiatric Clinical Hospital No. 1

Россия, 117152, Russia, Zagorodnoye shosse, 2

Nikolay A. Didkovsky

Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia

Author for correspondence.
Email: didkovskinic1@gmail.com
ORCID iD: 0000-0001-6567-5998
SPIN-code: 6146-5134
Scopus Author ID: 7004373221

PhD, MD, Doctor of Science (Medicine), Professor; Head of Laboratory of Clinical Immunology

Россия, 119435, Russia, Malaya Pirogovskaya st., 1A

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Copyright (c) Malashenkova I.K., Krynskiy S., Khailov N.A., Ratushnyy A.Y., Ogurtsov D.P., Chernyakova K.A., Anufrieva O.V., Goncharov D.B., Abbazova E.V., Baranets M.S., Andryushchenko A.V., Savilov V.B., Kostyuk G.P., Didkovsky N.A.

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