They have been shown to be important for host defense against various viruses, such as vesicular stomatitis virus, Sendai virus, hantavirus, reovirus, dengue virus, influenza virus, herpes simplex virus, and murine cytomegalovirus (1523)

They have been shown to be important for host defense against various viruses, such as vesicular stomatitis virus, Sendai virus, hantavirus, reovirus, dengue virus, influenza virus, herpes simplex virus, and murine cytomegalovirus (1523). investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs), such as DC-SIGN, heparan sulfate proteoglycan (HSPG), and 47 integrin, which mediate capture of HIV-1 on the cell surface. Intriguingly, following coculture with CD4+T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. Prior blocking with anti-HAF antibody or mannan before coculture impaired viraltrans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and these were required for efficient cell-to-cell HIV-1 transmission. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies MIM1 aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection. IMPORTANCEIn this study, we demonstrate the role of human mast cells isolated from mucosal tissues in mediating HIV-1trans-infection of CD4+T cells. This finding facilitates our understanding of HIV-1 mucosal infection and will benefit MIM1 the development of strategies to combat primary HIV-1 dissemination. == INTRODUCTION == Despite great advances in antiretroviral therapies, human immunodeficiency virus type 1 (HIV-1) infection still remains a major global epidemic. Sexual transmission is the principal route of HIV-1 acquisition, making the genital and rectal mucosae the major sites of viral transmission. The intestinal mucosa is also the primary site where HIV-1 amplifies to disseminate virus throughout the host and is critical in the early events in the establishment of infection and evasion of immune defenses. However , the mechanisms contributing to the establishment of HIV-1 primary infection remain largely unexplored. Cell-associated viral dissemination has been proposed to MIM1 play pivotal roles in HIV-1 primary infection, and multiple cell types, such as dendritic cells (DCs) and macrophages, have been reported to be hijacked by HIV-1 for local and systemic viral spread (14). DCs provide one of the best-described cell models for understanding cell-mediated HIV-1 capture and dissemination (1, 58). Mast cells are derived from hematopoietic progenitor cells and undergo final maturation in vascularized tissues. Mast cells are strategically in close contact with the host-environment interface, such as the skin, airway, gastrointestinal tract, and urinary tract. They express numerous pathogen-associated molecular patterns and play an important role in the early immunosurveillance for many pathogens (9, 10). Mast cells can interact with various immune cells in complex ways, including release of soluble factors and direct contact (11), and are important immune effector and modulatory cells that help to link innate and adaptive immunity in the fight against pathogens (9, 1214). They have been shown to be important for host defense against various viruses, such as vesicular stomatitis virus, Sendai virus, hantavirus, reovirus, dengue virus, influenza virus, herpes simplex virus, and murine cytomegalovirus (1523). MIM1 Additionally , mast cells can serve as antigen-presenting cells and participate in traditional immunologic synapse formation with T cells to mediate antigen-specific T cell activation (24). Although they are among the first cells at mucosal sites to encounter viruses, the role of mast cells in HIV-1 infection is poorly defined. The genital mucosae of HIV-infected women showed increased mast cell density, and increased numbers of mucosal mast cells were noted in men with AIDS-associated diarrhea (25, 26), suggesting a potential role for mast cells in HIV-1 infection. We hence investigated the potential contribution of mucosal mast cells to HIV-1 infection MIM1 and found that mast cells isolated from gut mucosal tissues express a variety of HIV-1 attachment factors (HAFs) and mediate capture of HIV-1 and the subsequent viraltrans-infection of CD4+T cells. Rabbit polyclonal to Smad2.The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene ‘mothers against decapentaplegic’ (Mad) and the C.elegans gene Sma. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. == MATERIALS AND METHODS == == Ethics statement. == Normal intestinal samples.