المؤلفون: Kruglov, Andrey A., Bondareva, Marina A., Gogoleva, Violetta S., Semin, Iaroslav K., Astrakhantseva, Irina V., Zvartsev, Ruslan, Lunin, Aleksandr S., Apolokhov, Vasiliy D., Shustova, Elena Yu, Volok, Viktor P., Ustyugov, Aleksey A., Ishmukhametov, Aydar A., Nedospasov, Sergei A., Kozlovskaya, Liubov I., Drutskaya, Marina S.

المساهمون: Ministry of Science and Higher Education of the Russian Federation, Russian Science Foundation

المصدر: European Journal of Immunology ; volume 54, issue 3 ; ISSN 0014-2980 1521-4141

الوصف: COVID‐19 is a systemic inflammatory disease initiated by SARS‐CoV‐2 virus infection. Multiple vaccines against the Wuhan variant of SARS‐CoV‐2 have been developed including a whole virion beta‐propiolactone‐inactivated vaccine based on the B.1.1 strain (CoviVac). Since most of the population has been vaccinated by targeting the original or early variants of SARS‐CoV‐2, the emergence of novel mutant variants raises concern over possible evasion of vaccine‐induced immune responses. Here, we report on the mechanism of protection by CoviVac, a whole virion‐based vaccine, against the Omicron variant. CoviVac‐immunized K18‐hACE2 Tg mice were protected against both prototype B.1.1 and BA.1‐like (Omicron) variants. Subsequently, vaccinated K18‐hACE2 Tg mice rapidly cleared the infection via cross‐reactive T‐cell responses and cross‐reactive, non‐neutralizing antibodies recognizing the Omicron variant Spike protein. Thus, our data indicate that efficient protection from SARS‐CoV‐2 variants can be achieved by the orchestrated action of cross‐reactive T cells and non‐neutralizing antibodies.

الإتاحة: https://doi.org/10.1002/eji.202350664Test

المؤلفون: Wen, Yi, Lu, Xiaohan, Privratsky, Jamie R., Ren, Jiafa, Ali, Saba, Yang, Bo, Rudemiller, Nathan P., Zhang, Jiandong, Nedospasov, Sergei A., Crowley, Steven D.

المساهمون: National Institute of Diabetes and Digestive and Kidney Diseases, U.S. Department of Veterans Affairs, National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province, VA Clinician Scientist Investigator Award

المصدر: Kidney360 ; volume 5, issue 1, page 44-56 ; ISSN 2641-7650

الوصف: Key Points Proximal tubular TNF aggravates kidney injury and fibrogenesis in aristolochic acid nephropathy. Tubular TNF disrupts the cell cycle in injured tubular epithelial cells. TNF-mediated toxic renal injury is independent of systemic immune responses. Background Aristolochic acid nephropathy (AAN) presents with tubular epithelial cell (TEC) damage and tubulointerstitial inflammation. Although TNF- α regulates cell apoptosis and inflammatory responses, the effects of tubular TNF in the progression of AAN require elucidation. Methods Floxed TNF mice on the 129/SvEv background were crossed with PEPCK-Cre mice to generate PEPCK-Cre + TNF flox/flox (TNF PTKO) mice or bred with Ksp-Cre mice to generate KSP-Cre + TNF flox/flox (TNF DNKO) mice. TNF PTKO, TNF DNKO, and wild-type controls (Cre negative littermates) were subjected to acute and chronic AAN. Results Deletion of TNF in the proximal but not distal nephron attenuated kidney injury, renal inflammation, and tubulointerstitial fibrosis after acute or chronic aristolochic acid (AA) exposure. The TNF PTKO mice did not have altered numbers of infiltrating myeloid cells in AAN kidneys. Nevertheless, kidneys from AA-treated TNF PTKO mice had reduced levels of proteins involved in regulated cell death, higher proportions of TECs in the G0/G1 phase, and reduced TEC proportions in the G2/M phase. Pifithrin- α , which restores the cell cycle, abrogated differences between the wild-type and PTKO cohorts in G2/M phase arrest of TECs and kidney fibrosis after AA exposure. Conclusions TNF from the proximal but not the distal nephron propagates kidney injury and fibrogenesis in AAN in part by inducing G2/M cell cycle arrest of TECs.

الإتاحة: https://doi.org/10.34067/kid.0000000000000314Test

المؤلفون: Gorshkova, Ekaterina A., Gubernatorova, Ekaterina O., Dvorianinova, Ekaterina M., Yurakova, Taisiya R., Marey, Maria V., Averina, Olga A., Holtze, Susanne, Hildebrandt, Thomas B., Dmitriev, Alexey A., Drutskaya, Marina S., Vyssokikh, Mikhail Yu., Nedospasov, Sergei A.

المساهمون: Russian Science Foundation

المصدر: Frontiers in Immunology ; volume 14 ; ISSN 1664-3224

الوصف: The naked mole-rat (NMR) is a unique long-lived rodent which is highly resistant to age-associated disorders and cancer. The immune system of NMR possesses a distinct cellular composition with the prevalence of myeloid cells. Thus, the detailed phenotypical and functional assessment of NMR myeloid cell compartment may uncover novel mechanisms of immunoregulation and healthy aging. In this study gene expression signatures, reactive nitrogen species and cytokine production, as well as metabolic activity of classically (M1) and alternatively (M2) activated NMR bone marrow-derived macrophages (BMDM) were examined. Polarization of NMR macrophages under pro-inflammatory conditions led to expected M1 phenotype characterized by increased pro-inflammatory gene expression, cytokine production and aerobic glycolysis, but paralleled by reduced production of nitric oxide (NO). Under systemic LPS-induced inflammatory conditions NO production also was not detected in NMR blood monocytes. Altogether, our results indicate that NMR macrophages are capable of transcriptional and metabolic reprogramming under polarizing stimuli, however, NMR M1 possesses species-specific signatures as compared to murine M1, implicating distinct adaptations in NMR immune system.

الإتاحة: https://doi.org/10.3389/fimmu.2023.1172467Test

المؤلفون: Gubernatorova, Ekaterina O., Gorshkova, Ekaterina A., Bondareva, Marina A., Podosokorskaya, Olga A., Sheynova, Anna D., Yakovleva, Anastasia S., Bonch-Osmolovskaya, Elizaveta A., Nedospasov, Sergei A., Kruglov, Andrey A., Drutskaya, Marina S.

المساهمون: Russian Science Foundation

المصدر: Frontiers in Immunology ; volume 14 ; ISSN 1664-3224

مصطلحات موضوعية: Immunology, Immunology and Allergy

الوصف: Akkermansia muciniphila is a gram-negative anaerobic bacterium, which represents a part of the commensal human microbiota. Decline in the abundance of A. muciniphila among other microbial species in the gut correlates with severe systemic diseases such as diabetes, obesity, intestinal inflammation and colorectal cancer. Due to its mucin-reducing and immunomodulatory properties, the use of probiotics containing Akkermansia sp. appears as a promising approach to the treatment of metabolic and inflammatory diseases. In particular, a number of studies have focused on the role of A. muciniphila in colorectal cancer. Of note, the results of these studies in mice are contradictory: some reported a protective role of A. muciniphila in colorectal cancer, while others demonstrated that administration of A. muciniphila could aggravate the course of the disease resulting in increased tumor burden. More recent studies suggested the immunomodulatory effect of certain unique surface antigens of A. muciniphila on the intestinal immune system. In this Perspective, we attempt to explain how A. muciniphila contributes to protection against colorectal cancer in some models, while being pathogenic in others. We argue that differences in the experimental protocols of administration of A. muciniphila , as well as viability of bacteria, may significantly affect the results. In addition, we hypothesize that antigens presented by pasteurized bacteria or live A. muciniphila may exert distinct effects on the barrier functions of the gut. Finally, A. muciniphila may reduce the mucin barrier and exerts combined effects with other bacterial species in either promoting or inhibiting cancer development.

الإتاحة: https://doi.org/10.3389/fimmu.2023.1303795Test

المؤلفون: Nedospasov, Sergei A., Drutskaya, Marina S., Kruglov, Andrey A.

المصدر: Molecular Biology of B Cells ; page 413-423 ; ISBN 9780323958950

الإتاحة: https://doi.org/10.1016/b978-0-323-95895-0.00008-8Test
https://api.elsevier.com/content/article/PII:B9780323958950000088?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:B9780323958950000088?httpAccept=text/plainTest

المؤلفون: Nosenko, Maxim, Anisov, Denis, Gubernatorova, Ekaterina, Gorshkova, Ekaterina, Zeng, Yi-Rong, Ye, Dan, Wang, Pu, Finlay, David, Drutskaya, Marina, Nedospasov, Sergei

المصدر: J Leukoc Biol ; ISSN:1938-3673

مصطلحات موضوعية: SDH, cytokines, immunometabolism

الوصف: Itaconate is one of the most studied immunometabolites produced by myeloid cells during inflammatory response. It mediates a wide range of anti-inflammatory and immunoregulatory effects and plays a role in a number of pathological states, including autoimmunity and cancer. Itaconate and its derivatives are considered as potential therapeutic agents for treatment of inflammatory diseases. While immunoregulatory effects of itaconate have been extensively studied in vitro and using knock-out mouse models, less is known about how therapeutic administration of this metabolite regulates inflammatory response in vivo. Here, we investigate the immunoregulatory properties of exogenous administration of itaconate (ITA) and its derivative dimethyl itaconate (DI) in a mouse model of LPS-induced inflammation. The data show that administration of ITA or DI controls systemic production of multiple cytokines, including increased IL-10 production. However, only DI was able to suppress systemic production of IFNγ and IL-1β. In contrast to in vitro data, administration of ITA or DI in vivo resulted in systemic upregulation of IL-6 in the blood. Electrophilic stress due to ITA or DI was not responsible for IL-6 upregulation. However, inhibition of SDH with dimethyl malonate (DM) also resulted in elevated systemic levels of IL-6 and IL-10. Taken together, our study reports a novel effect of exogenous itaconate and its derivative DI on the production of IL-6 in vivo, with important implications for the development of itaconate-based anti-inflammatory therapies.

العلاقة: https://doi.org/10.1093/jleuko/qiae149Test; https://pubmed.ncbi.nlm.nih.gov/38941443Test

الإتاحة: https://doi.org/10.1093/jleuko/qiae149Test
https://pubmed.ncbi.nlm.nih.gov/38941443Test

المؤلفون: Kruglov, Andrey A., Bondareva, Marina A., Gogoleva, Violetta S., Semin, Iaroslav K., Astrakhantseva, Irina V., Zvartsev, Ruslan, Lunin, Aleksandr S., Apolokhov, Vasiliy D., Shustova, Elena Yu, Volok, Viktor P., Ustyugov, Aleksey A., Ishmukhametov, Aydar A., Nedospasov, Sergei A., Kozlovskaya, Liubov I., Drutskaya, Marina S.

المصدر: European Journal of Immunology; Mar2024, Vol. 54 Issue 3, p1-17, 17p

مصطلحات موضوعية: SARS-CoV-2 Omicron variant, T cells, ANTIBODY formation, SARS-CoV-2, VIRUS diseases

مصطلحات جغرافية: WUHAN (China)

مستخلص: COVID‐19 is a systemic inflammatory disease initiated by SARS‐CoV‐2 virus infection. Multiple vaccines against the Wuhan variant of SARS‐CoV‐2 have been developed including a whole virion beta‐propiolactone‐inactivated vaccine based on the B.1.1 strain (CoviVac). Since most of the population has been vaccinated by targeting the original or early variants of SARS‐CoV‐2, the emergence of novel mutant variants raises concern over possible evasion of vaccine‐induced immune responses. Here, we report on the mechanism of protection by CoviVac, a whole virion‐based vaccine, against the Omicron variant. CoviVac‐immunized K18‐hACE2 Tg mice were protected against both prototype B.1.1 and BA.1‐like (Omicron) variants. Subsequently, vaccinated K18‐hACE2 Tg mice rapidly cleared the infection via cross‐reactive T‐cell responses and cross‐reactive, non‐neutralizing antibodies recognizing the Omicron variant Spike protein. Thus, our data indicate that efficient protection from SARS‐CoV‐2 variants can be achieved by the orchestrated action of cross‐reactive T cells and non‐neutralizing antibodies. [ABSTRACT FROM AUTHOR]

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المؤلفون: Yurakova, Taisiya R., Gubernatorova, Ekaterina O., Gorshkova, Ekaterina A., Nosenko, Maxim A., Nedospasov, Sergei A., Drutskaya, Marina S.

المساهمون: Suzhou University of Science and Technology, Russian Science Foundation, Russian Foundation for Basic Research, Ministry of Education and Science of the Russian Federation

المصدر: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ; volume 1868, issue 12, page 166531 ; ISSN 0925-4439

مصطلحات موضوعية: Molecular Biology, Molecular Medicine

الإتاحة: https://doi.org/10.1016/j.bbadis.2022.166531Test
https://api.elsevier.com/content/article/PII:S0925443922002022?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0925443922002022?httpAccept=text/plainTest

المؤلفون: Lechner, Antonie, Henkel, Fiona D.R., Hartung, Franziska, Bohnacker, Sina, Alessandrini, Francesca, Gubernatorova, Ekaterina O., Drutskaya, Marina S., Angioni, Carlo, Schreiber, Yannick, Haimerl, Pascal, Ge, Yan, Thomas, Dominique, Kabat, Agnieszka M., Pearce, Edward J., Ohnmacht, Caspar, Nedospasov, Sergei A., Murray, Peter J., Chaker, Adam M., Schmidt-Weber, Carsten B., Esser-von Bieren, Julia

المساهمون: German Research Foundation, Fritz Thyssen Stiftung, Helmholtz Association of German Research Centres

المصدر: Journal of Allergy and Clinical Immunology ; volume 149, issue 6, page 2078-2090 ; ISSN 0091-6749

الإتاحة: https://doi.org/10.1016/j.jaci.2021.11.026Test
https://api.elsevier.com/content/article/PII:S009167492102741X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S009167492102741X?httpAccept=text/plainTest

المؤلفون: Ninnemann, Justus, Winsauer, Caroline, Bondareva, Marina, Kühl, Anja A., Lozza, Laura, Durek, Pawel, Lissner, Donata, Siegmund, Britta, Kaufmann, Stefan H.E., Mashreghi, Mir-Farzin, Nedospasov, Sergei A., Kruglov, Andrey A.

المصدر: Mucosal Immunology ; volume 15, issue 4, page 698-716 ; ISSN 1933-0219

مصطلحات موضوعية: Immunology, Immunology and Allergy

الإتاحة: https://doi.org/10.1038/s41385-022-00506-xTest
https://www.nature.com/articles/s41385-022-00506-x.pdfTest
https://www.nature.com/articles/s41385-022-00506-xTest
https://api.elsevier.com/content/article/PII:S1933021922000939?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1933021922000939?httpAccept=text/plainTest