As mentioned above, pDCs arise not only from a myeloid precursor -the CDP- but also from a lymphoid precursor -the CLP-, giving this class of DCs a mixed ontogeny. such as TLR7, TLR9, and TLR3. Here, we discuss various types of dendritic cells found in humans and mice; their contribution to the activation of the antiviral response triggered by the secretion of IFN, through different routes of the induction for this important antiviral cytokine; and as to how DCs are involved in human infections that are considered highly frequent nowadays. Ly6C?B220?CD4?CD8+CD11bloCD11chiCD24hiCD205+ (DEC-205+)CD207+ (Langerin+)CLEC9A+XCR1+(33C36)Mouse cDC1 (CD103+)Lymphoid organs and Non-lymphoid organsMHC-II+Ly6C?B220?CD8?CD86+CD80+CD11b+CD11c+CD24+CD103+CD205+ (DEC-205+)CD207+ (Langerin+)XCR1+(37C43)Human cDC1 (CD141hi)Lymphoid organs and Non-lymphoid organsCD11cloCD45+CD141hi (BDCA-3hi)CLEC9A+XCR1+(44C46)Mouse cDC2 (CD11b+)Lymphoid organs and Non-lymphoid organsMHC-II+F4/80?CD4+CD11b+CD11c+CD24+CD64+CD103?CD172ahi (SIRPhi)XCR1lo/?(47, 48)Human cDC2 (CD1c+)Lymphoid organsMHC-II+CD1alo/+CD1c+ (BDCA-1+)CD11c+CD14?CD16?CD172a+ (SIRP+)XCR1?FcRI+CD207? (Langerin?)(47, 49C53)pDCsMouse pDCsBlood, lymph nodes and lymphoid tissuesMHC-IIloCD4+CD11b?B220+CD11cloCD25loCD38+CD40?CD43+CD62LmidLy6Chi(54C56)Human pDCsBlood and bone marrowMHC-IIloB220+CD1a?CD4+CD11a+CD11c?CD13?CD14?CD16?CD18+CD33?CD38loCD40loCD44+CD54+CD62L+CD123+ (IL-3R+)CD127? (IL-7R?)CD303+ (BDCA-2+)CD304+ (BDCA-4)(57C60) Open in a Ntn2l separate window Murine DCs Garcinone D Among the murine cDC1 subset, CD8+ DCs are of particular importance. As their name suggests, this class of DCs is characterized by the expression of a CD8 homodimer (distinct from the CD8+ T cell CD8 heterodimer) (37, 61), although no clear biological function has been attributed to it (62). CD8+ DCs reside in both central and peripheral lymphoid organs, namely thymus, spleen, and lymph nodes (62C64). Some of the PRRs expressed by this subset are TLR3, TLR9, and TLR11/12 (65C68), and unlike other DC subtypes, CD8+ DCs do not express TLR7 (68). These cells are capable of secreting large amounts of IL-12p70 upon activation (69), hence driving powerful TH1 responses when presenting antigens, and are specialized in cross-presentation of antigens on MHC-I molecules (70). These DCs are incapable of secreting interferon IFN-, although other DC subtypes do (69). Nonetheless, they are an important source of IFN- once they are activated via TLR3 (71). CD8+ DCs are characterized by surface expression of CD205, langerin (CD207), C-type lectin receptor 9A (CLEC9A), and chemokine receptor XCR1 (33C36) Finally, murine CD8+ DCs are also MHC-II+, CD4?, Ly6C?, CD11blo, CD11chi, CD24hi, and B220?. Another cDC1 subset relevant for the understanding of viral pathogenesis is the CD103+ DCs compartment, characterized by the expression of the E integrin CD103. These cells are present in many tissues, including the gut, lungs, spleen, skin, and various lymph nodes (38). CD103+ DCs have a developmental relation with CD8+ DCs (72) and Garcinone D share characteristic surface markers like CD24, CD205, and langerin (39C42). However, CD103+ DCs are capable of inducing a more robust TH17 response through IL-1 and IL-6 secretion (73), and lack the expression of TLR3, although they remain responsive to polyI:C, a TLR3 agonist (74). Immunophenotyping has revealed an extensive heterogeneity among CD103+ DCs, although some common features among each compartment are the expression of different surface markers such as Ly6C?, CD11b+, CD11c+, CD80+, CD86+, B220? and, of course, CD103+ Garcinone D (38). Most Garcinone D of them are CD8?, except for those that reside in the gut (namely, colon) (43) and spleen (37). Extensive murine subgroup immunophenotyping can be reviewed in del Rio et al. (38). Importantly, CD103+ DCs have enhanced antigen cross-presentation capacities, which is employed by the immune system for the resolution of some viral infections, as well as for the maintenance of self-tolerance and tumor immune control, since phagosome-derived peptides can be presented on MHC-I molecules to activate -or inhibit- cytotoxic CD8+ T cells (75, 76). Regarding viral infections, skin, and lung CD103+ DCs subtypes have been shown to prime Garcinone D CD8+ T.