MOLECULAR MIMICRY BETWEEN CHLAMYDIA PNEUMONIAE ANTIGENS AND PROTEINS INVOLVED IN ATHEROGENESIS AND ARTERITIDES WITH EXPERIMENTAL PATHOMORPHOLOGICAL CORRELATES



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Abstract

A series of epidemiological and experimental data suggest a link between Chlamydia pneumoniae and development of atherosclerosis as a variant of chronic productive inflammation of large and medium-sized arteries of the elastic and muscular-elastic types in response to accumulating atherogenic lipoprotein cholesterol. Atherogenesis consists of immunopathological and autoimmune components, being promoted in autoimmune vasculitis. Atherogenesis-related autoimmune manifestations may be enabled via molecular mimicry. The presence of homologous peptides between infectious agent antigens and human autoantigens may eventually activate autoreactive immune cells. The study investigated a relationship between Chlamydia pneumoniae, molecular mimicry, and development of atherosclerosis, a disease characterized by lipid accumulation and chronic inflammation of the arteries. Materials and Methods: We present a comprehensive bioinformatics analysis aimed at understanding the pathogenesis of atherosclerosis and arteritis by analyzing key antigenic proteins. Candidate protein amino acid sequences were retrieved from the UniProt and NCBI databases. The “Alignmentaj” application was used to identify mimicking pentapeptides. In addition, an infectious model of atherosclerosis was created using Chlamydia pneumoniae administered endotracheally to male rabbits. Pathohistological examination of animal aorta and carotid arteries was carried out. Results: Significant homology between chlamydial antigens and apoprotein B (84 pentapeptides) was revealed. Moreover, we found 23 mimicking pentapeptides in protein tenascin, which dually plays pathogenic and sanogenic role in atherogenesis. Fewer shared pentapeptides were identified in other autoantigens involved in atherogenesis and/or arteritis pathogenesis. Experimental chlamydial infection induced atherosclerotic changes in the aortic intima, including foam cell and plaque formation. The carotid artery wall had uniform thickness with preserved endothelium; however, degenerative changes and a mononuclear inflammatory infiltrates were observed in the vasa vasorum of the adventitia. Conclusion: Bioinformatic analysis underlines a potential for molecular mimicry as a mechanism of autoimmune atherogenic risk associated with Chlamydia infection. Experimental studies in rabbits confirmed the atherogenicity of Chlamydia infection and the induction of vasa vasorum vasculitis potentially due to mimicry between chlamydial antigens and atherogenic autoantigens.

About the authors

Leonid Pavlovich Churilov

Institute of Medicine, Saint Petersburg State University, St. Petersburg, Russia;
Saint Petersburg State University, St. Petersburg, Russia;
St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg, Russia

Email: elpach@mail.ru
ORCID iD: 0000-0001-6359-0026
SPIN-code: 8879-0875
Scopus Author ID: 6602953641
https://med.spbu.ru/kafedra-patologii/tpost/kg4myifgk1-churilov-leonid-pavlovich

M.D., Ph.D., Associate Professor, Head of the Department of Pathology

Russian Federation, 199034, Russia, St. Petersburg, Universitetskaya embk, bld. 7-9; 191036, Russia, St. Petersburg, Ligovsky prosp. Bld 2-4.

Tatiana Aleksandrovna Novitskaia

Institute of Medicine, Saint Petersburg State University, St. Petersburg, Russia;
Saint Petersburg State University, St. Petersburg, Russia

Email: nta0666@rambler.ru
SPIN-code: 2414-0069
https://med.spbu.ru/kafedra-patologii/tpost/am7t5paou1-novitskaya-tatyana-aleksandrovna

M.D., Ph.D., Associate Professor, Associate Professor of the Department of Pathology.

Russian Federation, 199034, Russia, St. Petersburg, Universitetskaya embk, bld. 7-9.

Muslimbek Ghulomovich Normatov

Institute of Medicine, Saint Petersburg State University, St. Petersburg, Russia;
Saint Petersburg State University, St. Petersburg, Russia

Email: muslimbek_normatov@mail.ru
ORCID iD: 0000-0002-1307-0513
SPIN-code: 9235-3589
Scopus Author ID: 57903483800
https://pureportal.spbu.ru/ru/persons/--(7dfebe33-a155-4476-9fe5-31a0e467b62e).html

postgraduate student, department of pathology

Russian Federation, 199034, Russia, St. Petersburg, Universitetskaya embk, bld. 7-9.

Valeriia Aleksandrovna Shapkina

Institute of Medicine, Saint Petersburg State University, St. Petersburg, Russia;
Saint Petersburg State University, St. Petersburg, Russia

Email: valshapkina@gmail.com
ORCID iD: 0000-0003-1843-2808
SPIN-code: 5353-0280
Scopus Author ID: 57383395600
https://pureportal.spbu.ru/ru/persons/--(188d71a1-3dec-47fa-9b01-7ac8e450f3dd).html

assistant, department of pathology

Russian Federation, 199034, Russia, St. Petersburg, Universitetskaya embk, bld. 7-9.

Pavel Petrovich Iablonskii

Saint Petersburg State University, St. Petersburg, Russia;
Clinic of High Technologies “Beloostrov”, Leningrad region, Vsevolozhsky distr., Yukkovskoye village, Russia

Author for correspondence.
Email: pavel.yablonski@gmail.com
ORCID iD: 0000-0002-0192-1931
SPIN-code: 6494-2319
Scopus Author ID: 56677646700
https://med.spbu.ru/kafedra-gospitalnoj-khirurgii/tpost/396ohklc71-yablonskii-pavel-petrovich

M.D., Ph.D., Associate Professor, Associate Professor of the Department of Hospital Surgery

Russian Federation, 199034, Russia, St. Petersburg, Universitetskaya embk, bld. 7-9; 188651, Russia, Leningrad region, Vsevolozhsky distr., Yukkovskoye village, bld. 1, corp.1.

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