Lymphocyte proliferation, mobility and longevity make them prime targets for virus infection. Myeloid cells that process and present environmental antigens to lymphocytes are consequently an important line of defence. Subcapsular sinus macrophages (SSMs) filter the afferent lymph and communicate with B-cells. How they interact with B-cell-tropic viruses is unknown. We analysed their encounter with murid herpesvirus-4 (MuHV-4), an experimentally accessible gammaherpesvirus related to Kaposi's sarcoma-associated herpesvirus. MuHV-4 disseminated via lymph nodes, and intranasally or subcutaneously inoculated virions readily infected SSMs. However, this infection was poorly productive. SSM depletion with clodronate-loaded liposomes or with diphtheria toxin in CD169-diphtheria toxin receptor transgenic mice increased B-cell infection and hastened virus spread to the spleen. Dendritic cells provided the main route to B-cells, and SSMs slowed host colonization, apparently by absorbing virions non-productively from the afferent lymph.
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http://dx.doi.org/10.1099/vir.0.000140 | DOI Listing |
Adv Sci (Weinh)
January 2025
SKKU Advanced Institute of Nanotechnology (SAINT), Department of Nano Engineering, Department of Nano Science and Technology, School of Chemical Engineering, Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea.
Despite their safety and widespread use, conventional protein antigen-based subunit vaccines face significant challenges such as low immunogenicity, insufficient long-term immunity, poor CD8 T-cell activation, and poor adaptation to viral variants. To address these issues, an infection-mimicking gel (IM-Gel) is developed that is designed to emulate the spatiotemporal dynamics of immune stimulation in acute viral infections through in situ supramolecular self-assembly of nanoparticulate-TLR7/8a (NP-TLR7/8a) and an antigen with tannic acid (TA). Through collagen-binding properties of TA, the IM-Gel enables sustained delivery and enhanced retention of NP-TLR7/8a and protein antigen in the lymph node subcapsular sinus of mice for over 7 days, prolonging the exposure of vaccine components in both B cell and T cell zones, leading to robust humoral and cellular responses.
View Article and Find Full Text PDFStem Cell Res Ther
November 2024
Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
Background: Mesenchymal stromal cell (MSC) therapy commonly involves systemic infusion of MSCs, which undergo apoptosis in the lung and induce immunoregulatory macrophages that reduce disease. The relevance of this mode of action, however, is yet to be determined for MSCs administered via other routes. Here, we administered MSCs via subcutaneous (SC) injection into inflamed tissue and investigated the immunomodulatory effects on the local lymph node (LN), which is a major site for the initiation and regulation of immune responses.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Kidney Disease Prevention and Control Technology, National Key Clinical Department of Kidney Diseases, Institute of Nephrology, Zhejiang University, Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, Zhejiang, 310003, P. R. China.
The establishment of a tolerant space to realize the co-stimulation of cytokines and contact-dependent molecules remain challenging in allotransplant. Here, an injectable genetically engineered hydrogel (iGE-Gel) is reported, which developed with a multivalent network of FOXP3 engineered extracellular vesicles (Foe-EVs) through the hydrophobic interaction between stearic acid modified hyaluronic acid (HASA) and the membrane phospholipids of extracellular vesicles (EVs). The iGE-Gel exhibited self-healing properties, injectability and biocompatibility.
View Article and Find Full Text PDFAdv Mater
November 2024
SKKU Advanced Institute of Nanotechnology (SAINT), Department of Nano Engineering, Department of Nano Science and Technology, School of Chemical Engineering, and Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea.
Biomech Model Mechanobiol
December 2024
School of Mathematics and Statistics, University of Glasgow, Glasgow, UK.
Lymph Nodes (LNs) are crucial to the immune and lymphatic systems, filtering harmful substances and regulating lymph transport. LNs consist of a lymphoid compartment (LC) that forms a porous bulk region, and a subcapsular sinus (SCS), which is a free-fluid region. Mathematical and mechanical challenges arise in understanding lymph flow dynamics.
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