PMID- 26474053 OWN - NLM STAT- MEDLINE DCOM- 20160603 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 10 DP - 2015 TI - Aging Impairs the Ability of Conventional Dendritic Cells to Cross-Prime CD8+ T Cells upon Stimulation with a TLR7 Ligand. PG - e0140672 LID - 10.1371/journal.pone.0140672 [doi] LID - e0140672 AB - The aging process is accompanied by altered immune system functioning and an increased risk of infection. Dendritic cells (DCs) are antigen-presenting cells that play a key role in both adaptive and innate immunity, but how aging affects DCs and their influence on immunity has not been thoroughly established. Here we examined the function of conventional DCs (cDCs) in old mice after TLR7 stimulation, focusing on their ability to cross-prime CD8+ T cells. Using polyU, a synthetic ssRNA analog, as TLR7 ligand and OVA as an antigen (Ag) model, we found that cDCs from old mice have a poor ability to stimulate a CD8+ T cell-mediated cytotoxic response. cDCs from old mice exhibit alterations in Ag-processing machinery and TLR7 activation. Remarkably, CD8alpha+ cDCs from old mice have an impaired ability to activate naive CD8+ T cells and, moreover, a lower capacity to mature and to process exogenous Ag. Taken together, our results suggest that immunosenescence impacts cDC function, affecting the activation of naive CD8+ T cells and the generation of effector cytotoxic T cells. FAU - Zacca, Estefania R AU - Zacca ER AD - Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, Argentina. FAU - Crespo, Maria I AU - Crespo MI AD - Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, Argentina. FAU - Acland, Rachel P AU - Acland RP AD - Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, Argentina. FAU - Roselli, Emiliano AU - Roselli E AD - Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, Argentina. FAU - Nunez, Nicolas G AU - Nunez NG AD - Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, Argentina. FAU - Maccioni, Mariana AU - Maccioni M AD - Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, Argentina. FAU - Maletto, Belkys A AU - Maletto BA AD - Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, Argentina. FAU - Pistoresi-Palencia, Maria C AU - Pistoresi-Palencia MC AD - Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, Argentina. FAU - Moron, Gabriel AU - Moron G AD - Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, Argentina. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151016 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antigens) RN - 0 (Membrane Glycoproteins) RN - 0 (Tlr7 protein, mouse) RN - 0 (Toll-Like Receptor 7) RN - 27416-86-0 (Poly U) SB - IM MH - Aging/*immunology MH - Animals MH - *Antigen Presentation MH - Antigens/immunology/pharmacology MH - CD8-Positive T-Lymphocytes/*enzymology MH - Cross-Priming/drug effects/*immunology MH - Dendritic Cells/*immunology MH - Female MH - *Immunity, Cellular MH - Membrane Glycoproteins/*immunology MH - Mice MH - Poly U/immunology/pharmacology MH - Toll-Like Receptor 7/*immunology PMC - PMC4608578 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/10/17 06:00 MHDA- 2016/06/04 06:00 PMCR- 2015/10/16 CRDT- 2015/10/17 06:00 PHST- 2015/07/21 00:00 [received] PHST- 2015/09/29 00:00 [accepted] PHST- 2015/10/17 06:00 [entrez] PHST- 2015/10/17 06:00 [pubmed] PHST- 2016/06/04 06:00 [medline] PHST- 2015/10/16 00:00 [pmc-release] AID - PONE-D-15-32037 [pii] AID - 10.1371/journal.pone.0140672 [doi] PST - epublish SO - PLoS One. 2015 Oct 16;10(10):e0140672. doi: 10.1371/journal.pone.0140672. eCollection 2015.