Immunology of SARS-CoV-2 Infection.

According to the data from the World Health Organization, about 800 million of the world population had contracted coronavirus infection caused by SARS-CoV-2 by mid-2023. Properties of this virus have allowed it to circulate in the human population for a long time, evolving defense mechanisms against the host immune system. Severity of the disease depends largely on the degree of activation of the systemic immune response, including overstimulation of macrophages and monocytes, cytokine production, and triggering of adaptive T- and B-cell responses, while SARS-CoV-2 evades the immune system actions.

Biology of the SARS-CoV-2 Coronavirus.

New coronavirus infection causing COVID-19, which was first reported in late 2019 in China, initiated severe social and economic crisis that affected the whole world. High frequency of the errors in replication of RNA viruses, zoonotic nature of transmission, and high transmissibility allowed betacoronaviruses to cause the third pandemic in the world since the beginning of 2003: SARS-CoV in 2003, MERS-CoV in 2012, and SARS-CoV-2 in 2019. The latest pandemic united scientific community and served as a powerful impetus in the study of biology of coronaviruses: new routes of virus penetration into the human cells were identified, features of the replication cycle were studied, and new functions of coronavirus proteins were elucidated.

Prevalence and Incidence of Upper Respiratory Tract Infection Events Are Elevated Prior to the Development of Rheumatoid Arthritis in First-Degree Relatives.

The aim of this study was to characterize infection events in a longitudinal cohort of first-degree relatives (FDR) of probands with rheumatoid arthritis (RA) and explore their associations with RA development. To this end, newly diagnosed RA patients ( = 283), unaffected related FDR and age-matched healthy women were ascertained from the Caucasian triple women prospective Tatarstan cohort. In this cohort initiated in 1997, 26/283 (9.

Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportunity in Cystic Fibrosis.

(R)-Roscovitine, a pharmacological inhibitor of kinases, is currently in phase II clinical trial as a drug candidate for the treatment of cancers, Cushing's disease and rheumatoid arthritis. We here review the data that support the investigation of (R)-roscovitine as a potential therapeutic agent for the treatment of cystic fibrosis (CF). (R)-Roscovitine displays four independent properties that may favorably combine against CF: (1) it partially protects F508del-CFTR from proteolytic degradation and favors its trafficking to the plasma membrane; (2) by increasing membrane targeting of the TRPC6 ion channel, it rescues acidification in phagolysosomes of CF alveolar macrophages (which show abnormally high pH) and consequently restores their bactericidal activity; (3) its effects on neutrophils (induction of apoptosis), eosinophils (inhibition of degranulation/induction of apoptosis) and lymphocytes (modification of the Th17/Treg balance in favor of the differentiation of anti-inflammatory lymphocytes and reduced production of various interleukins, notably IL-17A) contribute to the resolution of inflammation and restoration of innate immunity, and (4) roscovitine displays analgesic properties in animal pain models.

TRPC6 channel translocation into phagosomal membrane augments phagosomal function.

Defects in the innate immune system in the lung with attendant bacterial infections contribute to lung tissue damage, respiratory insufficiency, and ultimately death in the pathogenesis of cystic fibrosis (CF). Professional phagocytes, including alveolar macrophages (AMs), have specialized pathways that ensure efficient killing of pathogens in phagosomes. Phagosomal acidification facilitates the optimal functioning of degradative enzymes, ultimately contributing to bacterial killing.

A transient peak of infections during onset of rheumatoid arthritis: a 10-year prospective cohort study.

Objectives: The role of infection in rheumatoid arthritis (RA) has not been determined. We aimed to document the infectious burden and some aspects of antibacterial immunity in a large and prospective cohort study of RA patients in the early and late stages of the disease and in their relatives predisposed to RA.

Setting: Clinical and laboratory examination of all individuals enrolled in the study was performed in the Republican Clinical Hospital, Kazan, Russia.

RhoA/ROCK downregulates FPR2-mediated NADPH oxidase activation in mouse bone marrow granulocytes.

Polymorphonuclear neutrophils (PMNs) express the high and low affinity receptors to formylated peptides (mFPR1 and mFPR2 in mice, accordingly). RhoA/ROCK (Rho activated kinase) pathway is crucial for cell motility and oxidase activity regulated via FPRs. There are contradictory data on RhoA-mediated regulation of NADPH oxidase activity in phagocytes.

Mononuclear Phagocytes in Rheumatoid Arthritis Patients and their Relatives - Family Similarity.

Unlabelled: The aim of this work was to study the peripheral blood monocyte functions in patients with advanced RA and their predisposed to RA relatives in comparison with those in women, not hereditary tainted with autoimmune diseases (donors). In groups comprising 24 RA patients, 24 relatives, and 24 donors the following monocyte functions were assessed: engulfment and digestion (radioisotope method); release of lysosomal glucuronidase in response to opsonized zymosan (fluorescent method); reactive oxygen species (ROS) generation (chemiluminescence), and serum levels of proinflammatory cytokines (ELISA). The monocyte specific feature in patients and their relatives is chiefly extracellular digestion due to the delayed engulfment.