Dendritic cells (DCs) are one of the primary cells that recognize incoming viruses at the mucosal portals of entry. APC functions as a potent dissemination strategy in Vilazodone D8 different anatomical compartments. to cell-surface molecules, which is what usually happens with shorter Siglecs that are also expressed by DCs [19,23,31]. In vivo, the role of Siglec-1 during viral infection has been mostly studied in murine models, focusing on resident tissue macrophages that express this lectin and play key immunomodulatory functions. Vilazodone D8 Siglec-1-expressing macrophages are located in the subcapsular sinus of the lymph nodes, and they protect mice against vesicular stomatitis pathogen (VSV) disease by including incoming viruses. Viral sensing causes cytokine promotes and launch antigen demonstration to B cells [32,33]. However, research using different retroviruses to infect mice show that the protecting function of the macrophages could be hijacked for effective viral disease and dissemination within cells. Indeed, robust disease of a specific retrovirus in lymphoid cells and spleen needs Siglec-1-expressing macrophages . The pathogenicity from the infecting retrovirus is paramount to tip the total amount of the Siglec-1-expressing macrophages in favor of the protective immune function. The antiviral response dominates when the replicating virus has an expanded tropism , as it also happens in the case of the amphotropic VSV contamination [32,33]. Under these pathogenic conditions, viral capture via Siglec-1 macrophages is necessary to elicit an effective antiviral CD8+ T cell response via antigen cross-presentation by DCs . Overall, these murine studies explain how Siglec-1 can contain viral replication and induce antiviral immunity against highly pathogenic viruses, but also favor viral spread within tissues when retroviruses have a limited tropism. Yet, how these findings correlate with the pathogenesis of different Siglec-1-interacting human viruses, such as HIV-1 or EBOV, remains largely unexplored. HIV-1 is the causative agent of acquired immunodeficiency syndrome (AIDS), a pandemic that has affected more than 70 million people worldwide , while EBOV is responsible for the intermittent outbreaks that produce a filovirus-associated disease (FVD) with high fatality rates . In this review, we discuss how Siglec-1 is usually induced on human DCs upon viral contamination, to what degree that impacts different viral antigen presentation routes, and in which ways distant enveloped viruses have evolved to exploit Siglec-1 function as a dissemination strategy in distinct Vilazodone D8 anatomical compartments. 2. Viral Sensing and Immune Activation Triggers Siglec-1 Induction on DCs Siglec-1 is a receptor codified by an interferon-stimulated gene and is therefore potently upregulated on distinct human DCs, monocytes, and macrophages when these cells sense type I interferons (IFNs) such as IFN [38,39,40]. Thus, contamination with viruses such as HIV-1 or EBOV upregulates Siglec-1 appearance on APCs firmly, as they straight cause or indirectly promote the discharge of type I IFNs via immune system activating elements (Body 1). Open up in another window Body 1 Systems of Siglec-1 upregulation during individual immunodeficiency pathogen (HIV)-1 and Ebola pathogen (EBOV) attacks. (A) HIV-1 induces secretion of type I interferons (IFNs) by plasmacytoid DCs (pDCs) through Toll-like receptor (TLR) -7 and -9 sensing, which upregulates Siglec-1 on DCs within a paracrine way. Furthermore, lipopolysaccharide (LPS) from bacterial translocation upregulates Siglec-1 on DCs via TLR4 sensing and autocrine type I IFN discharge. (B) During EBOV infections, type I IFNs might play a central function in enhancing Vilazodone D8 Siglec-1 appearance on DCs also, although this requirements further investigation. pDCs may make type I IFNs in response to EBOV infections in vivo, while bacterial translocation was suspected during a case of gram-negative septicemia in an EBOV-infected patient. In parallel, viral components such as secreted EBOV glycoprotein may induce activation of myeloid cells through TLR4 signaling, providing an alternative stimulus of autocrine type I IFNs during EBOV contamination. While solid arrows indicate established mechanisms, dotted arrows suggest processes that Rabbit Polyclonal to OR1A1 require further investigation. IFNAR: IFN/ receptor; sGP: secreted glycoprotein. In the case of HIV-1 contamination, IFN levels are potently boosted during acute contamination, and sustainedalthough to a lower extentthroughout the chronic stage, which is characterized by a persistent immune activation [41,42,43]. Several DC types have been identified as the sources of IFN production during the course of HIV-1 infection, and therefore contribute to Siglec-1 induction. Plasmacytoid DCs (pDCs) are considered the most potent type I IFN suppliers in blood , and their capacity to secrete IFN in response to HIV-1 sensing continues to be confirmed in vitro [45,46,47,48,49] and in vivo [50,51,52], both through the chronic and severe stages of the condition [50,51,53]. Of take note, pDC.