The Sphingosine-1-Phosphate (S1P) Lysophospholipid Receptor S1P3 Regulates MAdCAM-1+ Endothelial Cells in Splenic Marginal Sinus Organization

Marginal zones (MZs) are microdomains in the spleen that contain various types of immune cells, including MZ B cells, MOMA1+ metallophilic macrophages, and mucosal addressin cell adhesion molecule 1 (MAdCAM-1)+ endothelial cells. MAdCAM-1+ and MOMA1+ cells line the sinus, that separates MZs from splenic follicles. Here we show that a receptor for the lysophospholipid sphingosine-1-phosphate (S1P), S1P3, is required for normal numbers of splenic immature and MZ B cells, and for S1P-induced chemotaxis of MZ B cells. S1P3 is also essential for proper alignment of MOMA1+ macrophages and MAdCAM-1+ endothelial cells along the marginal sinus. The lack of cohesion of the marginal sinus in S1P3−/− mice affects MZ B cell functions, as wild-type (WT) MZ B cells migrate more into S1P3−/− follicles than into WT follicles after treatment with lipopolysaccharide. Additionally, short-term homing experiments demonstrate that WT MZ B cells home to the S1P3−/− spleen in increased numbers, suggesting a role for the marginal sinus in regulating MZ B cells numbers. Moreover, S1P3−/− mice are defective in mounting immune responses to thymus-independent antigen type 2 due to defects in radiation-resistant cells in the spleen. These data identify lysophospholipids and the S1P3 receptor as essential regulators of the MZ sinus and its role as a barrier to the follicle

Cytokines and MMP-9 Levels in rheumatoid arthritis and osteoarthritis patients with persistent parvovirus B19, HHV-6 and HHV-7 Infection

Funding Information: This work was supported in part by the grant Nr. 09.0112 from Latvian Council of Science and by the National Research Programme in Biomedicine 2014–2017. Publisher Copyright: © 2019 Anda Kadiša et al., published by Sciendo 2019. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes erosive changes and ankylosis of joints and may cause internal injuries. Osteoarthritis (OA) is a degenerative process of the articular cartilage. However, inflammatory mediators may play a pivotal role in the initiation and perpetuation of the OA process. It is necessary to continue to study possible factors that may promote the development of the disease. The goal of this study was to evaluate the frequency and activity stage of parvovirus B19 (B19V) and persistent human herpes virus (HHV)-6 and HHV-7 infection in RA and OA patients, and healthy persons, in relation to cytokine levels and presence or absence of viral infections. RA patients with active B19V infection had the highest levels of tumour necrosis factor alpha (TNF-α), which may contribute to the development of RA. In the case of OA, the TNF-α level was higher in patients with active persistent B19V infection, suggesting that B19V reactivation affects also OA. Interleukin (IL)-6, IL-10 and metalloproteinase (MMP)-9 levels were higher in RA patients with latent HHV-6/-7 infection in comparison with active HHV-6/-7 infection, whereas in OA patients levels of all studied cytokines were very variable, ranging from low to high but without significant differences. This suggests that also latent HHV-6 and -7 viral infections can promote development of RA.Peer reviewe

Presence of Human Bocavirus 1 in Hospitalised Children with Acute Respiratory Tract Infections in Latvia and Lithuania

Funding Information: This study was supported by Republic of China (Taiwan)-Republic of Latvia-Republic of Lithuania scientific collaboration project, "Establishing of the framework to track molecular epidemiology of Parvoviruses and to correlate sequence variability with different clinical manifestations" (Research Council of Latvia Nr. gr. 6-25/2012/0026, Research Council of Lithuania TAPLLT02/201) and by project Nr. RSU ZP 17/2013 "Epidemiology, pathogenicity of human Bocavirus (HBoV) species and possible association with lower respiratory tract illnesses and acute gastroenteritis in children". We are grateful to Rita Nikitenkiene and Irina Maksimova for technical help. Publisher Copyright: © 2016 by Zaiga Nora-Krūkle. Copyright: Copyright 2016 Elsevier B.V., All rights reserved.Human bocavirus 1 (HBoV1) is a parvovirus recently found to be a possible aetiologic agent of acute respiratory disease in children. We conducted the first clinical and molecular study on this virus in Latvia (LV) and Lithuania (LT). The aim of the study was to determine the occurrence of HBoV1 in respiratory tract samples taken from hospitalised children with acute respiratory tract infections in LV and LT. In total 186 children with age one to 50 months, and who fulfilled criteria of acute respiratory tract infection, including lower respiratory tract infections, with or without fever, were included in this study. A nasopharyngeal aspirate was obtained from each patient on admission. DNA was isolated and polimerase chain reaction (PCR) performed targeting the HBoV1 NS1sequence. HBoV1 positive samples were sequenced and phylogenetic analysis was performed. HBoV1 sequence was detected in 42 (32%) of 130 LV and in 8 (14%) of 56 LT samples. In LV the majority of patients with HBoV1 infection were observed in February while in LT in October. The phylogenetic tree for HBoV1 indicated that isolates of HBoV1 cluster closely and include almost all of the isolates in this study. HBoV1 is common in Latvia and Lithuania and might be a significant pathogen that contributes to acute respiratory tract infections in children.Peer reviewe

Microtubules control cellular shape and coherence in amoeboid migrating cells

Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How a cell surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid cell migration by locally promoting the retraction of protrusions. In migrating dendritic cells, local microtubule depolymerization within protrusions remote from the microtubule organizing center triggers actomyosin contractility controlled by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin localization, thereby causing two effects that rate-limit locomotion: (1) impaired cell edge coordination during path finding and (2) defective adhesion resolution. Compromised shape control is particularly hindering in geometrically complex microenvironments, where it leads to entanglement and ultimately fragmentation of the cell body. We thus demonstrate that microtubules can act as a proprioceptive device: they sense cell shape and control actomyosin retraction to sustain cellular coherence

A Rapid ELISA Test for Detection of Human Paraproteins

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Increased Numbers of CD4+CD25+ and CD8+CD25+ T-Cells in Peripheral Blood of Patients with Rheumatoid Arthritis with Parvovirus B19 Infection

Aim: To investigate T-cell subpopulations in peripheral blood of human parvovirus B19 DNA-positive (B19+) and-negative (B19-) patients with rheumatoid arthritis (RA) and healthy persons. Patients and Methods: Blood samples were collected from 115 patients with RA and 47 healthy volunteers; 27 patients with RA and nine controls were B19+. Cluster of differentiation (CD) 4, 8, 25 and 45RA were analyzed on blood cells. CD25 expression on CD4+CD45RA+, CD4+CD45RA-, CD8+CD45RA+, CD8+CD45RA- subsets were analyzed by flow cytometry. Results: The percentage of CD25low and CD25hi cells was increased on CD4+CD45RA+, CD4+CD45RA-T-cells and the percentage of CD25+ cells was increased on CD8+CD45RA+, CD8+CD45RA-T-cells of B19+ patients with RA in comparison with B19- patients and controls. Conclusion: Raised levels of CD4 and CD8 regulatory T-cells in B19+ RA patients could cause downregulation of antiviral clearance mechanisms and lead to activation of persistent human parvovirus B19 infection in patients with RA.publishersversionPeer reviewe