Optimal Generation of Tissue-Resident but Not Circulating Memory T Cells during Viral Infection Requires Crosspriming by DNGR-1+Dendritic Cells.
Despite the crucial role of tissue-resident memory T (Trm) cells in protective immunity, their priming remains poorly understood. Here, we have shown differential priming requirements for Trm versus circulating memory CD8+T cells. In vaccinia cutaneous-infected mice, DNGR-1-mediated crosspresentation was required for optimal Trm cell priming but not for their skin differentiation or for circulating memory T cell generation. DNGR-1+dendritic cells (DCs) promoted T-bet transcription-factor induction and retention of CD8+T cells in the lymph nodes (LNs). Inhibition of LN egress enhanced Trm cell generation, whereas genetic or antibody blockade of DNGR-1 or specific signals provided during priming by DNGR-1+DCs, such as interleukin-12 (IL-12), IL-15, or CD24, impaired Trm cell priming. DNGR-1 also regulated Trm cell generation during influenza infection. Moreover, protective immunity depended on optimal Trm cell induction by DNGR-1+DCs. Our results reveal specific priming requirements for CD8+Trm cells during viral infection and vaccination.
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid, 28029, Spain. Electronic address: siborra@cnic.es.
Salvador
S
Iborra
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid, 28029, Spain.
María
M
Martínez-López
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid, 28029, Spain.
Sofía C
SC
Khouili
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid, 28029, Spain.
Michel
M
Enamorado
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid, 28029, Spain; Department of Biochemistry, Faculty of Medicine, Universidad Autónoma de Madrid, Calle Arzobispo Morcillo 4, Madrid, 28029, Spain.
Francisco J
FJ
Cueto
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid, 28029, Spain.
Ruth
R
Conde-Garrosa
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid, 28029, Spain.
Carlos
C
Del Fresno
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid, 28029, Spain. Electronic address: dsancho@cnic.es.
David
D
Sancho
D000818:Animals; D051927:CD24 Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000276:immunology*; D012867:Skin / Q000276:immunology / Q000821:virology; D014615:Vaccinia / Q000276:immunology / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology* / Q000821:virology
D051927:CD24 Antigen; C529914:Clec9a protein, mouse; D019409:Interleukin-15; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D018664:Interleukin-12
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