PMID- 38474410 OWN - NLM STAT- MEDLINE DCOM- 20240314 LR - 20240315 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 13 IP - 5 DP - 2024 Mar 3 TI - Exploiting Leishmania-Primed Dendritic Cells as Potential Immunomodulators of Canine Immune Response. LID - 10.3390/cells13050445 [doi] LID - 445 AB - Dendritic cells (DCs) capture pathogens and process antigens, playing a crucial role in activating naive T cells, bridging the gap between innate and acquired immunity. However, little is known about DC activation when facing Leishmania parasites. Thus, this study investigates in vitro activity of canine peripheral blood-derived DCs (moDCs) exposed to L. infantum and L. amazonensis parasites and their extracellular vesicles (EVs). L. infantum increased toll-like receptor 4 gene expression in synergy with nuclear factor kappaB activation and the generation of pro-inflammatory cytokines. This parasite also induced the expression of class II molecules of major histocompatibility complex (MHC) and upregulated co-stimulatory molecule CD86, which, together with the release of chemokine CXCL16, can attract and help in T lymphocyte activation. In contrast, L. amazonensis induced moDCs to generate a mix of pro- and anti-inflammatory cytokines, indicating that this parasite can establish a different immune relationship with DCs. EVs promoted moDCs to express class I MHC associated with the upregulation of co-stimulatory molecules and the release of CXCL16, suggesting that EVs can modulate moDCs to attract cytotoxic CD8(+) T cells. Thus, these parasites and their EVs can shape DC activation. A detailed understanding of DC activation may open new avenues for the development of advanced leishmaniasis control strategies. FAU - Valerio-Bolas, Ana AU - Valerio-Bolas A AUID- ORCID: 0000-0002-0273-4353 AD - Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal. FAU - Meunier, Mafalda AU - Meunier M AD - Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal. FAU - Palma-Marques, Joana AU - Palma-Marques J AD - Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal. FAU - Rodrigues, Armanda AU - Rodrigues A AUID- ORCID: 0000-0003-4261-3879 AD - Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal. FAU - Santos, Ana Margarida AU - Santos AM AD - Divisao de Medicina Veterinaria, Guarda Nacional Republicana, 1200-771 Lisbon, Portugal. FAU - Nunes, Telmo AU - Nunes T AD - Microscopy Center, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal. FAU - Ferreira, Rui AU - Ferreira R AD - Banco de Sangue Animal (BSA), 4100-462 Porto, Portugal. FAU - Armada, Ana AU - Armada A AD - Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal. FAU - Alves, Joao Carlos AU - Alves JC AUID- ORCID: 0000-0002-1329-3709 AD - Divisao de Medicina Veterinaria, Guarda Nacional Republicana, 1200-771 Lisbon, Portugal. FAU - Antunes, Wilson AU - Antunes W AD - Unidade Militar Laboratorial de Defesa Biologica e Quimica (UMLDBQ), 1849-012 Lisbon, Portugal. FAU - Cardoso, Ines AU - Cardoso I AD - Banco de Sangue Animal (BSA), 4100-462 Porto, Portugal. FAU - Mesquita-Gabriel, Sofia AU - Mesquita-Gabriel S AD - Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal. FAU - Lobo, Lis AU - Lobo L AD - Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal. FAU - Alexandre-Pires, Graca AU - Alexandre-Pires G AUID- ORCID: 0000-0002-9462-4679 AD - CIISA, Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1649-004 Lisbon, Portugal. AD - Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1200-771 Lisbon, Portugal. FAU - Marques, Luis AU - Marques L AD - BioSystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisbon-FCUL-BioISI Ce3CE, 1749-016 Lisbon, Portugal. FAU - Pereira da Fonseca, Isabel AU - Pereira da Fonseca I AUID- ORCID: 0000-0002-6632-1224 AD - CIISA, Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1649-004 Lisbon, Portugal. AD - Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1200-771 Lisbon, Portugal. FAU - Santos-Gomes, Gabriela AU - Santos-Gomes G AUID- ORCID: 0000-0001-9264-3887 AD - Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal. LA - eng GR - PTDC/CVT-CVT/28908/2017 (http://doi.org/10.54499/PTDC/CVT-CVT/28908/2017)/Fundacao para a Ciencia e Tecnologia/ GR - PTDC/CVT-CVT/0228/2020 (http://doi.org/10.54499/PTDC/CVT-CVT/0228/2020)/Fundacao para a Ciencia e Tecnologia/ GR - Centro de Investigacao Interdisciplinar em Sanidade Animal (CIISA, UIDB/00276/2020)/Fundacao para a Ciencia e Tecnologia/ GR - Global Health and Tropical Medicine (GHTM, UID/04413/2020)/Fundacao para a Ciencia e Tecnologia/ GR - LA-REAL - LA/P/0117/2020/Fundacao para a Ciencia e Tecnologia/ PT - Journal Article DEP - 20240303 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Adjuvants, Immunologic) RN - 0 (Cytokines) SB - IM MH - Animals MH - Dogs MH - *Leishmania MH - CD8-Positive T-Lymphocytes MH - Dendritic Cells MH - Adjuvants, Immunologic/metabolism MH - Cytokines/metabolism MH - Lymphocyte Activation PMC - PMC10931270 OTO - NOTNLM OT - L. infantum OT - Leishmania amazonensis OT - Leishmania extracellular vesicles OT - cytokines OT - dog OT - innate immunity OT - major histocompatibility complex OT - pattern recognition receptors OT - peripheral blood-derived dendritic cells (moDCs) COIS- The authors declare no conflicts of interest. EDAT- 2024/03/13 06:46 MHDA- 2024/03/14 06:46 PMCR- 2024/03/03 CRDT- 2024/03/13 01:25 PHST- 2024/01/05 00:00 [received] PHST- 2024/02/23 00:00 [revised] PHST- 2024/02/26 00:00 [accepted] PHST- 2024/03/14 06:46 [medline] PHST- 2024/03/13 06:46 [pubmed] PHST- 2024/03/13 01:25 [entrez] PHST- 2024/03/03 00:00 [pmc-release] AID - cells13050445 [pii] AID - cells-13-00445 [pii] AID - 10.3390/cells13050445 [doi] PST - epublish SO - Cells. 2024 Mar 3;13(5):445. doi: 10.3390/cells13050445.