106 results on '"Martín-Gayo, Enrique"'
Search Results
2. Tyrosine kinase 2 modulates splenic B cells through type I IFN and TLR7 signaling
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Bodega-Mayor, Irene, Delgado-Wicke, Pablo, Arrabal, Alejandro, Alegría-Carrasco, Estíbaliz, Nicolao-Gómez, Ana, Jaén-Castaño, Marta, Espadas, Cristina, Dopazo, Ana, de Luis, Enrique Vázquez, Martín-Gayo, Enrique, Gaspar, María Luisa, de Andrés, Belén, and Fernández-Ruiz, Elena
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- 2024
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3. T regulatory lymphocytes specific for SARS-CoV-2 display increased functional plasticity
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Esparcia-Pinedo, Laura, Lancho-Sánchez, Ángel, Tsukalov, Ilya, Pacheco, María I., Martínez-Fleta, Pedro, Pérez-Miés, Belén, Palacios-Calvo, José, Sánchez-Madrid, Francisco, Martín-Gayo, Enrique, and Alfranca, Arantzazu
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- 2023
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4. Antiretroviral therapy duration and immunometabolic state determine efficacy of ex vivo dendritic cell-based treatment restoring functional HIV-specific CD8+ T cells in people living with HIV
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Calvet-Mirabent, Marta, Sánchez-Cerrillo, Ildefonso, Martín-Cófreces, Noa, Martínez-Fleta, Pedro, de la Fuente, Hortensia, Tsukalov, Ilya, Delgado-Arévalo, Cristina, Calzada, María José, de los Santos, Ignacio, Sanz, Jesús, García-Fraile, Lucio, Sánchez-Madrid, Francisco, Alfranca, Arantzazu, Muñoz-Fernández, María Ángeles, Buzón, Maria J., and Martín-Gayo, Enrique
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- 2022
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5. Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker
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Lozano-Prieto, Marta, Adlam, David, García-Guimaraes, Marcos, Sanz-García, Ancor, Vera-Tomé, Paula, Rivero, Fernando, Cuesta, Javier, Bastante, Teresa, Baranowska-Clarke, Anna A., Vara, Alicia, Martin-Gayo, Enrique, Vicente-Manzanares, Miguel, Martín, Pilar, Samani, Nilesh J, Sánchez-Madrid, Francisco, Alfonso, Fernando, and de la Fuente, Hortensia
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- 2021
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6. IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study
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Alvarado, Teresa, Martínez, Pablo, Javier de la Cuerda Llorente, Francisco, Arco, Carmen del, Aguilar, Juan Mariano, Villalba, Natalia, Negro, Mónica, Contreras, Elvira, Rey, Ana del, Santiago, Cristina, Junquera, Manuel, Caminero, Raquel, Val, Francisco Javier, González, Sonia, Caño, Marta, López, Isabel, von Wernitz, Andrés, Retana, Bárbara, Guerra, Iñigo, Sorando, Jorge, Chao, Lydia, Cárdenas, María José, Espiga, Verónica, Chicharro, Pablo, Rodríguez, Pedro, Alday, Iñigo Hernando, Sampedro, Miguel, Prada, Jorge, Aldama, Eukene Rojo, Real, Yolanda, Caldas, María, Casabona, Sergio, Lanas-Gimeno, Aitor, Camara, Rafael de la, Alvárez, Angela Figuera, Aguadol, Beatriz, Morell, Alberto, Ramírez, Esther, Zurriaga, Amparo Ibáñez, Abanades, María Pérez, García, Silvia Ruiz, Aranda, Tomás Gallego, Ruiz, María, Nieto, Concepción Martínez, Serra, José María, Sánchez-Madrid, Francisco, Muñoz-Calleja, Cecilia, Alfranca, Arantzazu, Aspa, Javier, Marcos-Jiménez, Ana, Sánchez-Alonso, Santiago, Alcaraz-Serna, Ana, Mateu-Albero, Tamara, Sánchez-Cerrillo, Ildefonso, Esparcia, Laura, Martínez-Fleta, Pedro, López-Sanz, Celia, Gabrie, Ligia, Guerola, Luciana del Campo, Fernández, Elena, Calzada, M<ce:sup loc='post"><ce:underline>a</ce:underline></ce:sup> José, Tejedor, Reyes, Canabal, Alfonso, Albert, Patricia, Rodríguez-Serrano, Diego A., Iglesias, Judit, Suarez, Fernando, Sánchez, Juan Antonio, Abad, Beatriz, Suarez, Carmen, Santos, Ignacio de los, Galván-Román, José María, Roy, Emilia, Rodríguez-Cortes, Pablo, García-Fraile, Lucio, Sanz, Jesus, Sanchez, Eduardo, Moldenhauer, Fernando, Casado, Pedro, Curbelo, Jose, Gutierrez, Angela, Bautista, Azucena, Giménez, Nuria Ruiz, Fernandez, Angelica, Parra, Pedro, Moyano, Berta, Barrios, Ana, Real de Asua, Diego, Sanchez, Beatriz, Saez, Carmen, Ciudad, Marianela, Navas, Desiré, Domingo, Laura Cardeñoso, Torresano, María del Carmen Cuevas, García, Diego Domingo, Cavero, Teresa Alarcón, Blanco, Alicia García, Ramírez, Alexandra Martín, Semiglia Chong, María Auxiliadora, Cobos, Ainhoa Gutiérrez, Zurita Cruz, Nelly Daniela, Fraile Torres, Arturo Manuel, Sanchez-Gonzalez, Carmen, Perpén, Antonio Fernádez, Pérez, Carolina Díaz, Ancochea, Julio, Alonso, Tamara, Landete, Pedro, Soriano, Joan, Cisneros, Carolina, Castillo, Elena García, García Pérez, Francisco Javier, Girón, Rosa María, Marcos, Celeste, Zamora, Enrique, García, Patricia García, Castañeda, Santos, García-Vicuña, Rosario, González-Álvaro, Isidoro, Rodríguez-García, Sebastián, Fernández-Díaz, Carlos, Cubas, Irene Llorente, Tomero, Eva G., Castañeda, Noelia García, Ortiz, Ana M<ce:sup loc='post"><ce:underline>a</ce:underline></ce:sup>, Valero, Cristina, Uriarte, Miren, Montes, Nuria, Rodríguez-García, Sebastián C., Roy-Vallejo, Emilia, del Campo Guerola, Luciana, Suárez-Fernández, Carmen, del Arco, Carmen, de los Santos, Ignacio, de la Cámara, Rafael, Soriano, Joan B., Martín-Gayo, Enrique, Fraile Torres, Arturo, and Cardeñoso, Laura
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- 2021
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7. Effects of first-line antiretroviral therapy on the CD4/CD8 ratio and CD8 cell counts in CoRIS: a prospective multicentre cohort study
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Jarrin, Inmaculada, Moreno, Santiago, Alejos, Belén, Muñoz-Fernández, MÁngeles, Consuegra, Irene, Merino, Esperanza, García, Gema, Lirola, Ana López, García, Dácil, Asensi, Víctor, Valle, Eulalia, Rubio, Rafael, Pulido, Federico, Iribarren, José Antonio, Arrizabalaga, Julio, Gutiérrez, Félix, Masiá, Mar, Muga, Roberto, Sanvisens, Arantza, Berenguer, Juan, Vidal, Francesc, Montero, Marta, Blanco, José Ramón, López Bernarlo de Quirós, Juan Carlos, González-Garcia, Juan, Peraire, Joaquín, Arazo, Piedad, López-Aldeguer, José, Dalmau, David, Arnalich, Francisco, Rivero, Maria, Oteo, José Antonio, Sampériz, Gloria, Amengual, María José, Jaén, Angels, de los Santos, Ignacio, Repáraz, Jesús, Navarro, Gemma, Bernal, Enrique, Sanz, Jesús, Viciana, Pompeyo, García, Federico, Casado, José Luis, Del Romero, Jorge, Cano, Alfredo, Antela, Antonio, Quero, José Hernández, Riera, Melchor, Raposo, Montserrat, Santos, Jesús, Losada, Elena, Daniel, Podzamczer, Peñaranda, María, Ayerbe, Cristina Gómez, Espinosa, Nuria, Olalla, Julián, Imaz, Arkaitz, Martínez, Onofre, Curran, Adrian, Castro, Ángeles, Pérez Stachowski, Javier, Muñoz, Josefa, Vera, Francisco Jesús, Galera, Carlos, Pernas, Berta, Amador, Concha, Zuriñe, Miren, Albendin, Helena, Suárez-García, Inés, Pasquau, Francisco, Omar, Mohamed, Malmierca, Eduardo, de Zarraga, Miguel Alberto, Gómez Vidal, María Amparo, Estrada, Vicente, Górgolas, Miguel, Sanz, José, Téllez, María Jesús, Galindo, María José, Cabello, Alfonso, Rivero, Antonio, Arranz, Alberto, Cervero, Miguel, Vilalta, Ramón, Pineda, Juan A, Rivero-Juárez, Antonio, Torres, Rafael, Poveda, Eva, Rincón, Pilar, Pérez, Alexandre, Moreno, Cristina, Portilla, Irene, Díaz-Flores, Felicitas, Rivas, María E, Bisbal, Otilia, Aramburu, María J, Padilla, Sergio, Fuster, Daniel, Gutiérrez, Isabel, Viladés, Consuelo, Blanes, Marino, Arribas, José Ramón, Ibarra, Valvanera, Sanmartí, Montse, de Alda, María Ruiz, Cervantes, Manel, Salas, Ana, Dronda, Fernando, Alcaraz, Antonia, Muñoz, Leopoldo, Rodríguez, Carmen, Ribas, María Angels, Viciana, Isabel, López-Cortés, Luis, Tiraboschi, Juan, del Arco, Alfonso, Martínez, Lorena, Mena, Álvaro, Mirena, Josu, Pérez, Aurora, Ena, Javier, González-Ruano, Patricia, Vergas, Jorge, Álvarez, Beatriz, Hernández, Cristina, Ferrer, Ana, López, Pedro, Macías, Juan, Crespo, Manuel, Navarro, Maria Luisa, Iniesta, Carlos, Agea, Iván, Gómez, Juan Luis, Suárez-Zarracina, Tomás, Hernando, Asunción, Camino, Xabier, Robledano, Catalina, Ramírez, Margarita, Veloso, Sergio, Tasias, María, Bernardino, Jose Ignacio, Metola, Luis, Cairó, Mireia, de León Cano, María Teresa, Calzado, Sonia, Sarria, Cristina, Moreno, Ana, Bravo, Joaquín, Alvarez, Marta, Puerta, Teresa, Campins, Antoni A, Palacios, Rosario, Silva, Ana, de la Torre, Javier, García, Josefina, Ibarra, Sofía, Iborra, Asunción, Benito, Concha, Martín, Dolores, Pérez-Somarriba, Juncal, Prieto, Laura, Novella, María, Machuca, Isabel, Merchante, Nicolás, Morano, Luis, González, Maria Isabel, García, Luis NM, Portilla, Joaquín, Alonso, María del Mar, Pérez, Laura, Domínguez, Lourdes, Rodríguez-Arrondo, Francisco, Colomé, Joan Gregori, Padilla, Belén, Vargas, Montserrat, Castro, Iván, Castro, Juan Miguel, Sanz, Mercedes, Martinez-Lacasa, Javier, Pierola, Beatriz, Navarro, Marta, Garcia-Fraile, Lucio, Pérez-Elias, Maria Jesús, Muñoz, Ángeles, Chueca, Natalia, Carrió, Juan Carlos, Vidal, Carmen, Pérez, Carmen, Saumoy, María, Prada, José Luis, Alcaraz, Begoña, Ferrero, Oscar, Moreno, Antonio, Fenoll, Vicenta, Ruiz, Mª Pilar, Frias, Mario, Real, Luis Miguel, Miralles, Celia, Garcia, Federico, Sanz, Nieves, Sánchez-Payá, José, Pelazas, Ricardo, Rial, David, von Wichman, Miguel Ángel, Adsuar, Araceli, Gijón, Paloma, Olona, Montserrat, Calabuig, Eva, Delgado, Ana, Pérez-Martínez, Laura, Velli, Pablo, Martín-Gayo, Enrique, Gutiérrez, Carolina, Alcaraz, Maria José, Vinuesa, David, Vera, Mar, Fanjul, Francisco, Gonzalez-Domenec, Carmen, Prieto, Paula, de las Lomas, José N García, Jimeno, Amaya, López, Josefina, Merlos, Maria, Gil, Concepción, Camacho, Angela, Corma, Anais, Ocampo, Antonio, Rava, Marta, Rodríguez, Juan Carlos, Hernández, Jehovana, Bermejo, Laura, Pascual, Lidia, Pascual, Rafael, Aldamiz-Echevarría, Teresa, Rull, Anna, Cuéllar, Sandra, Escosa, Luis, Font, Roser, Madrid, Nadia, del Carmen Villalba, Maria, Martinez-Montes, Clara, Ballesteros, Juan, Murillas, Javier, Cámara, María Mar, Vidal, Asunción, Algado, José Tomas, Fernández, Marta, Pousada, Guillermo, Iribarren, Jose Antonio, Gimeno, Lina, Alemán, María Remedios, Santacreu, Mireia, Goenaga, Miguel Ángel, Tejerina, Francisco, Rodríguez-Gallego, Esther, Salavert, Miguel, Herranz, Pedro, Martinez, Marina, del Campo, Santos, Guerrero, Carlos, Ayerdi, Oskar, Homar, Francisco, de la Peña, Mireia, Meca, Marisa, Díez, Marcos, Azkune, Harkaitz, Barber, Xavier, Balsalobre, Pascual, Castellanos, Alfonso Javier, García-Bujalance, Silvia, Vivancos, Maria Jesús, Fuentes, Ana, Martin, Maria Luisa, Lopez, Iñigo, Vilchez, Helem, Lopez, Miriam, Carreres, Melissa, Ibarguren, Maialen, Agullo, Vanessa, Diez, Cristina, López-Dupla, Miguel, García, Milagros, Umerez, Maitane, Martínez-Sanz, Javier, Payeras, Antoni, Reus, Sergio, Lizardi, Aitziber, Garcia, Javier, Pérez, Leire, González-Baeza, Alicia, Anxa, Usua, González, Juan, Boix, Vicente, Kortajarena, Xabier, Pascual, Reyes, Fanciulli, Chiara, Martín-Carbonero, Maria Luz, Mellado, Maria José, Micán, Rafael, Montejano, Rocio, Montes, María Luisa, Moreno, Victoria, Pérez-Valero, Ignacio, Rúa, Guadalupe, Rodés, Berta, Sainz, Talia, Sendagorta, Elena, Stella, Natalia, Valencia, Eulalia, Velasco, Tamara, Muñoz-Fernández, María Ángeles, Torrús, Diego, Carmona, María Pilar, Roca, María, Mayoral, Mario, Vallejo, Alejandro, Serrano-Villar, Sergio, Ron, Raquel, Talavera-Rodríguez, Alba, Fernández-Felix, Borja M, Herrera, Sabina, Muriel, Alfonso, de Zárraga, Miguel Alberto, and Vivancos, María J
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- 2020
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8. Effective innate immune response in natural HIV-1 controllers. Can mimicking lead to novel preventive and cure strategies against HIV-1?
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Calvet-Mirabent, Marta and Martín-Gayo, Enrique
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- 2022
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9. Immunological Fingerprints of Controllers Developing Neutralizing HIV-1 Antibodies
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Martin-Gayo, Enrique, Gao, Ce, Chen, Hsiao Rong, Ouyang, Zhengyu, Kim, Dhohyung, Kolb, Kellie E., Shalek, Alex K., Walker, Bruce D., Lichterfeld, Mathias, and Yu, Xu G.
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- 2020
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10. Imbalance of SARS-CoV-2-specific CCR6+ and CXCR3+ CD4+ T cells and IFN-γ + CD8+ T cells in patients with Long-COVID
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Martínez-Fleta, Pedro, Marcos, María Celeste, Jimenez-Carretero, Daniel, Galván-Román, José María, Girón-Moreno, Rosa María, Calero-García, Ana Adela, Arcos-García, Ana, Martín-Gayo, Enrique, de la Fuente, Hortensia, Esparcia-Pinedo, Laura, Aspa, Javier, Ancochea, Julio, Alfranca, Arantzazu, and Sánchez-Madrid, Francisco
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- 2024
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11. KLRG1 expression on natural killer cells is associated with HIV persistence, and its targeting promotes the reduction of the viral reservoir
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Astorga-Gamaza, Antonio, primary, Perea, David, additional, Sanchez-Gaona, Nerea, additional, Calvet-Mirabent, Marta, additional, Gallego-Cortés, Ana, additional, Grau-Expósito, Judith, additional, Sanchez-Cerrillo, Ildefonso, additional, Rey, Joan, additional, Castellví, Josep, additional, Curran, Adrian, additional, Burgos, Joaquin, additional, Navarro, Jordi, additional, Suanzes, Paula, additional, Falcó, Vicenç, additional, Genescà, Meritxell, additional, Martín-Gayo, Enrique, additional, and Buzon, Maria J., additional
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- 2023
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12. Extracellular vesicles from Listeria monocytogenes-infected dendritic cells alert the innate immune response
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Izquierdo-Serrano, Raúl, primary, Fernández-Delgado, Irene, additional, Moreno-Gonzalo, Olga, additional, Martín-Gayo, Enrique, additional, Calzada-Fraile, Diego, additional, Ramírez-Huesca, Marta, additional, Jorge, Inmaculada, additional, Camafeita, Emilio, additional, Abián, Joaquín, additional, Vicente-Manzanares, Miguel, additional, Veiga, Esteban, additional, Vázquez, Jesús, additional, and Sánchez-Madrid, Francisco, additional
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- 2022
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13. Dendritic cells: Nearly 40 years later…
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Benitez-Ribas, Daniel, Borràs, Francesc E., del Val, Margarita, Lasarte, Juan José, Marañón, Concepción, Martín-Gayo, Enrique, Sarobe, Pablo, Toribio, Maria L., and Montoya, María
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- 2012
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14. Development of an Effective Immune Response in Adults With Down Syndrome After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination
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Esparcia-Pinedo, Laura, primary, Yarci-Carrión, Ayla, additional, Mateo-Jiménez, Gloria, additional, Ropero, Noelia, additional, Gómez-Cabañas, Laura, additional, Lancho-Sánchez, Ángel, additional, Almendro-Vázquez, Patricia, additional, Martín-Gayo, Enrique, additional, Paz-Artal, Estela, additional, Sanchez-Madrid, Francisco, additional, Moldenhauer, Fernando, additional, Gutiérrez-Cobos, Ainhoa, additional, Real de Asúa, Diego, additional, and Alfranca, Arantzazu, additional
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- 2022
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15. Supplementary Material Extracellular vesicles from Listeria monocytogenes-infected dendritic cells alert the innate immune response
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Izquierdo-Serrano, Raúl, Fernández-Delgado, Irene, Moreno-Gonzalo, Olga, Martín-Gayo, Enrique, Calzada-Fraile, Diego, Ramírez-Huesca, Marta, Jorge, Inmaculada, Camafeita, Emilio, Abián, Joaquín, Vicente-Manzanares, Miguel, Veiga, Esteban, Vázquez, Jesús, Sánchez-Madrid, Francisco, Izquierdo-Serrano, Raúl, Fernández-Delgado, Irene, Moreno-Gonzalo, Olga, Martín-Gayo, Enrique, Calzada-Fraile, Diego, Ramírez-Huesca, Marta, Jorge, Inmaculada, Camafeita, Emilio, Abián, Joaquín, Vicente-Manzanares, Miguel, Veiga, Esteban, Vázquez, Jesús, and Sánchez-Madrid, Francisco
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- 2022
16. DataSheet_1_Extracellular vesicles from Listeria monocytogenes-infected dendritic cells alert the innate immune response.pdf [Dataset]
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Izquierdo-Serrano, Raúl, Fernández-Delgado, Irene, Moreno-Gonzalo, Olga, Martín-Gayo, Enrique, Calzada-Fraile, Diego, Ramírez-Huesca, Marta, Jorge, Inmaculada, Camafeita, Emilio, Abián, Joaquín, Vicente-Manzanares, Miguel, Veiga, Esteban, Vázquez, Jesús, Sánchez-Madrid, Francisco, Izquierdo-Serrano, Raúl, Fernández-Delgado, Irene, Moreno-Gonzalo, Olga, Martín-Gayo, Enrique, Calzada-Fraile, Diego, Ramírez-Huesca, Marta, Jorge, Inmaculada, Camafeita, Emilio, Abián, Joaquín, Vicente-Manzanares, Miguel, Veiga, Esteban, Vázquez, Jesús, and Sánchez-Madrid, Francisco
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- 2022
17. Extracellular vesicles from Listeria monocytogenes-infected dendritic cells alert the innate immune response
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Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Fundación Ramón Areces, Fundación la Caixa, Instituto de Salud Carlos III, European Commission, Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares (España), Ministerio de Ciencia e Innovación (España), Centro Nacional de Investigaciones Cardiovasculares (España), Izquierdo-Serrano, Raúl, Fernández-Delgado, Irene, Moreno-Gonzalo, Olga, Martín-Gayo, Enrique, Calzada-Fraile, Diego, Ramírez-Huesca, Marta, Jorge, Inmaculada, Camafeita, Emilio, Abián, Joaquín, Vicente-Manzanares, Miguel, Veiga, Esteban, Vázquez, Jesús, Sánchez-Madrid, Francisco, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Fundación Ramón Areces, Fundación la Caixa, Instituto de Salud Carlos III, European Commission, Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares (España), Ministerio de Ciencia e Innovación (España), Centro Nacional de Investigaciones Cardiovasculares (España), Izquierdo-Serrano, Raúl, Fernández-Delgado, Irene, Moreno-Gonzalo, Olga, Martín-Gayo, Enrique, Calzada-Fraile, Diego, Ramírez-Huesca, Marta, Jorge, Inmaculada, Camafeita, Emilio, Abián, Joaquín, Vicente-Manzanares, Miguel, Veiga, Esteban, Vázquez, Jesús, and Sánchez-Madrid, Francisco
- Abstract
Communication through cell-cell contacts and extracellular vesicles (EVs) enables immune cells to coordinate their responses against diverse types of pathogens. The function exerted by EVs in this context depends on the proteins and nucleic acids loaded into EVs, which elicit specific responses involved in the resolution of infection. Several mechanisms control protein and nucleic acid loading into EVs; in this regard, acetylation has been described as a mechanism of cellular retention during protein sorting to exosomes. HDAC6 is a deacetylase involved in the control of cytoskeleton trafficking, organelle polarity and cell migration, defense against Listeria monocytogenes (Lm) infection and other immune related functions. Here, we show that the protein content of dendritic cells (DCs) and their secreted EVs (DEVs) vary during Lm infection, is enriched in proteins related to antiviral functions compared to non-infected cells and depends on HDAC6 expression. Analyses of the post-translational modifications revealed an alteration of the acetylation and ubiquitination profiles upon Lm infection both in DC lysates and DEVs. Functionally, EVs derived from infected DCs upregulate anti-pathogenic genes (e.g. inflammatory cytokines) in recipient immature DCs, which translated into protection from subsequent infection with vaccinia virus. Interestingly, absence of Listeriolysin O in Lm prevents DEVs from inducing this anti-viral state. In summary, these data underscore a new mechanism of communication between bacteria-infected DC during infection as they alert neighboring, uninfected DCs to promote antiviral responses.
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- 2022
18. CD4+ T Cell Immune Specificity Changes After Vaccination in Healthy And COVID-19 Convalescent Subjects
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Instituto de Salud Carlos III, European Commission, Cooperativa de Viviendas Buen Suceso, Red de Investigación Cardiovascular (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), La Caixa, Banco Santander, Conferencia de Rectores de las Universidades Españolas, Comunidad de Madrid, Consejo Superior de Investigaciones Científicas (España), Esparcia-Pinedo, Laura, Martinez-Fleta, Pedro, Ropero, Noelia, Vera-Tomé, Paula, Reyburn, H. T., Casasnovas, José María, Rodríguez-Frade, José Miguel, Valés-Gómez, Mar, Vilches, Carlos, Martín-Gayo, Enrique, Muñoz-Calleja, Cecilia, Sánchez-Madrid, Francisco, Alfranca, Arántzazu, Instituto de Salud Carlos III, European Commission, Cooperativa de Viviendas Buen Suceso, Red de Investigación Cardiovascular (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), La Caixa, Banco Santander, Conferencia de Rectores de las Universidades Españolas, Comunidad de Madrid, Consejo Superior de Investigaciones Científicas (España), Esparcia-Pinedo, Laura, Martinez-Fleta, Pedro, Ropero, Noelia, Vera-Tomé, Paula, Reyburn, H. T., Casasnovas, José María, Rodríguez-Frade, José Miguel, Valés-Gómez, Mar, Vilches, Carlos, Martín-Gayo, Enrique, Muñoz-Calleja, Cecilia, Sánchez-Madrid, Francisco, and Alfranca, Arántzazu
- Abstract
The immune response promoted by SARS-CoV-2 vaccination is relevant to develop novel vaccines and optimized prevention strategies. We analyzed the adaptive immunity in healthy donors (HD) and convalescent individuals (CD), before and after administering BNT162b2 vaccine. Our results revealed specific changes in CD4+ T cell reactivity profile in vaccinated HD and CD, with an increase in S1 and S2 positive individuals, proportionally higher for S2. On the contrary, NCAP reactivity observed in HD and CD patients was no longer detectable after vaccination. Despite the substantial antibody response in CD, MPro-derived peptides did not elicit CD4+ lymphocyte activation in our assay in either condition. HD presented an increment in anti-S and anti-RBD IgG after first dose vaccination, which increased after the second vaccination. Conversely, anti-S and anti-RBD IgG and IgA titers increased in already positive CD after first dose administration, remaining stable after second dose inoculation. Interestingly, we found a strong significant correlation between S1-induced CD4+ response and anti-S IgA pre-vaccination, which was lost after vaccine administration.
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- 2022
19. Development of an Effective Immune Response in Adults With Down Syndrome After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination.
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Esparcia-Pinedo, Laura, Yarci-Carrión, Ayla, Mateo-Jiménez, Gloria, Ropero, Noelia, Gómez-Cabañas, Laura, Lancho-Sánchez, Ángel, Almendro-Vázquez, Patricia, Martín-Gayo, Enrique, Paz-Artal, Estela, Sanchez-Madrid, Francisco, Moldenhauer, Fernando, Gutiérrez-Cobos, Ainhoa, Asúa, Diego Real de, and Alfranca, Arantzazu
- Subjects
COVID-19 ,IMMUNIZATION ,DOWN syndrome ,COVID-19 vaccines ,IMMUNE system ,ANTIBODY formation ,DESCRIPTIVE statistics ,DATA analysis software ,PHENOTYPES - Abstract
Background Immune dysregulation in individuals with Down syndrome (DS) leads to an increased risk for hospitalization and death due to coronavirus disease 2019 (COVID-19) and may impair the generation of protective immunity after vaccine administration. Methods The cellular and humoral responses of 55 individuals with DS who received a complete SARS-CoV-2 vaccination regime at 1 to 3 (visit [V 1]) and 6 (V2) months were characterized. Results SARS-CoV-2–reactive CD4+ and CD8+ T lymphocytes with a predominant Th1 phenotype were observed at V1 and increased at V2. Likewise, an increase in SARS-CoV-2–specific circulating Tfh (cTfh) cells and CD8+ CXCR5+ PD-1hi lymphocytes was already observed at V1 after vaccine administration. Specific immunoglobulin G (IgG) antibodies against SARS-CoV-2 S protein were detected in 96% and 98% of subjects at V1 and V2, respectively, although IgG titers decreased significantly between both time points. Conclusions Our findings show that DS individuals develop an effective immune response to usual regimes of SARS-CoV-2 vaccination. [ABSTRACT FROM AUTHOR]
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- 2023
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20. Plasmacytoid dendritic cells resident in human thymus drive natural Treg cell development
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Martín-Gayo, Enrique, Sierra-Filardi, Elena, Corbí, Angel L., and Toribio, María L.
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- 2010
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21. The novel RUNX3/p33 isoform is induced upon monocyte-derived dendritic cell maturation and downregulates IL-8 expression
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Puig-Kröger, Amaya, Aguilera-Montilla, Noemi, Martínez-Nuñez, Rocío, Domínguez-Soto, Angeles, Sánchez-Cabo, Fátima, Martín-Gayo, Enrique, Zaballos, Angel, Toribio, María L., Groner, Yoram, Ito, Yoshiaki, Dopazo, Ana, Corcuera, María T., Alonso Martín, María J., Vega, Miguel A., and Corbí, Angel L.
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- 2010
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22. CD4+ T Cell Immune Specificity Changes After Vaccination in Healthy And COVID-19 Convalescent Subjects
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Esparcia-Pinedo, Laura, primary, Martínez-Fleta, Pedro, additional, Ropero, Noelia, additional, Vera-Tomé, Paula, additional, Reyburn, Hugh T., additional, Casasnovas, José M., additional, Rodríguez Frade, José M., additional, Valés-Gómez, Mar, additional, Vilches, Carlos, additional, Martín-Gayo, Enrique, additional, Muñoz-Calleja, Cecilia, additional, Sanchez-Madrid, Francisco, additional, and Alfranca, Arantzazu, additional
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- 2022
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23. Development of an effective immune response in adults with Down Syndrome after SARS-CoV-2 vaccination
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Esparcia-Pinedo, Laura, primary, Yarci-Carrión, Ayla, additional, Mateo-Jiménez, Gloria, additional, Ropero, Noelia, additional, Gómez-Cabañas, Laura, additional, Lancho-Sánchez, Ángel, additional, Martín-Gayo, Enrique, additional, Sanchez-Madrid, Francisco, additional, Moldenhauer, Fernando, additional, Gutiérrez-Cobos, Ainhoa, additional, de Asúa, Diego Real, additional, and Alfranca, Arantzazu, additional
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- 2022
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24. A Differential Signature of Circulating miRNAs and Cytokines Between COVID-19 and Community-Acquired Pneumonia Uncovers Novel Physiopathological Mechanisms of COVID-19
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Martínez-Fleta, Pedro, primary, Vera-Tomé, Paula, additional, Jiménez-Fernández, María, additional, Requena, Silvia, additional, Roy-Vallejo, Emilia, additional, Sanz-García, Ancor, additional, Lozano-Prieto, Marta, additional, López-Sanz, Celia, additional, Vara, Alicia, additional, Lancho-Sánchez, Ángel, additional, Martín-Gayo, Enrique, additional, Muñoz-Calleja, Cecilia, additional, Alfranca, Arantzazu, additional, González-Álvaro, Isidoro, additional, Galván-Román, José María, additional, Aspa, Javier, additional, de la Fuente, Hortensia, additional, and Sánchez-Madrid, Francisco, additional
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- 2022
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25. Poly I:C and STING agonist‐primed DC increase lymphoid tissue polyfunctional HIV‐1‐specific CD8+ T cells and limit CD4+ T‐cell loss in BLT mice
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Calvet‐Mirabent, Marta, primary, Claiborne, Daniel T., additional, Deruaz, Maud, additional, Tanno, Serah, additional, Serra, Carla, additional, Delgado‐Arévalo, Cristina, additional, Sánchez‐Cerrillo, Ildefonso, additional, de los Santos, Ignacio, additional, Sanz, Jesús, additional, García‐Fraile, Lucio, additional, Sánchez‐Madrid, Francisco, additional, Alfranca, Arantzazu, additional, Muñoz‐Fernández, María Ángeles, additional, Allen, Todd M., additional, Buzón, Maria J., additional, Balazs, Alejandro, additional, Vrbanac, Vladimir, additional, and Martín‐Gayo, Enrique, additional
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- 2022
- Full Text
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26. Circulating miRNAs and Cytokines Uncover Novel Physiopathological Mechanisms of COVID-19
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Martínez-Fleta, Pedro, primary, Vera-Tomé, Paula, additional, Jiménez-Fernández, María, additional, Requena, Silvia, additional, Roy-Vallejo, Emilia, additional, Sanz-García, Ancor, additional, Lozano-Prieto, Marta, additional, López-Sanz, Celia, additional, Vara, Alicia, additional, Lancho-Sánchez, Ángel, additional, Martín-Gayo, Enrique, additional, Muñoz-Calleja, Cecilia, additional, Alfranca, Arantzazu, additional, González-Álvaro, Isidoro, additional, Galván-Román, José María, additional, Aspa, Javier, additional, Fuente, Hortensia de la, additional, and Sanchez-Madrid, Francisco, additional
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- 2021
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27. TAILORED DC INDUCE PROTECTIVE HIV-1 SPECIFIC POLYFUNCTIONAL CD8+ T CELLS IN THE LYMPHOID TISSUE FROM HUMANIZED BLT MICE
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Calvet-Mirabent, Marta, primary, Claiborne, Daniel T., additional, Deruaz, Maud, additional, Tanno, Serah, additional, Serra, Carla, additional, Delgado-Arévalo, Cristina, additional, Sánchez-Cerrillo, Ildefonso, additional, de los Santos, Ignacio, additional, Sanz, Jesús, additional, García-Fraile, Lucio, additional, Sánchez-Madrid, Francisco, additional, Alfranca, Arantzazu, additional, Muñoz-Fernández, María Ángeles, additional, Allen, Todd M., additional, Buzón, Maria J., additional, Balazs, Alejandro, additional, Vrbanac, Vladimir, additional, and Martín-Gayo, Enrique, additional
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- 2021
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28. Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker
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Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares (España), Fundación BBVA, Fundación la Caixa, Instituto de Salud Carlos III, Comunidad de Madrid, British Heart Foundation, NIHR Biomedical Research Centre (UK), Lozano-Prieto, Marta, Adlam, David, García-Guimaraes, Marcos, Sanz-García, Ancor, Vera-Tomé, Paula, Rivero, Fernando, Cuesta, Javier, Bastante, Teresa, Baranowska-Clarke, Anna A., Vara, Alicia, Martín-Gayo, Enrique, Vicente-Manzanares, Miguel, Martín, Pilar, Samani, Nilesh J., Sánchez-Madrid, Francisco, Alfonso, Fernando, Fuente, Hortensia de la, Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares (España), Fundación BBVA, Fundación la Caixa, Instituto de Salud Carlos III, Comunidad de Madrid, British Heart Foundation, NIHR Biomedical Research Centre (UK), Lozano-Prieto, Marta, Adlam, David, García-Guimaraes, Marcos, Sanz-García, Ancor, Vera-Tomé, Paula, Rivero, Fernando, Cuesta, Javier, Bastante, Teresa, Baranowska-Clarke, Anna A., Vara, Alicia, Martín-Gayo, Enrique, Vicente-Manzanares, Miguel, Martín, Pilar, Samani, Nilesh J., Sánchez-Madrid, Francisco, Alfonso, Fernando, and Fuente, Hortensia de la
- Abstract
[Background]: Spontaneous Coronary Artery Dissection (SCAD) is an important cause of acute coronary syndromes, particularly in young to middle-aged women. Differentiating acute SCAD from coronary atherothrombosis remains a major clinical challenge. [Methods]: A case-control study was used to explore the usefulness of circulating miRNAs to discriminate both clinical entities. The profile of miRNAs was evaluated using an unbiased human RT-PCR platform and confirmed using individual primers. miRNAs were evaluated in plasma samples from acute SCAD and atherothrombotic acute myocardial infarction (AT-AMI) from two independent cohorts; discovery cohort (SCAD n = 15, AT-AMI n = 15), and validation cohort (SCAD n = 11, AT-AMI n = 41) with 9 healthy control subjects. Plasma levels of IL-8, TGFB1, TGBR1, Endothelin-1 and MMP2 were analysed by ELISA assays. [Findings]: From 15 differentially expressed miRNAs detected in cohort 1, we confirmed in cohort 2 the differential expression of 4 miRNAs: miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p, whose expression was higher in SCAD compared to AT-AMI. The combined expression of these 4 miRNAs showed the best predictive value to distinguish between both entities (AUC: 0.879, 95% CI 0.72–1.0) compared to individual miRNAs. Functional profiling of target genes identified an association with blood vessel biology, TGF-beta pathway and cytoskeletal traction force. ELISA assays showed high plasma levels of IL-8, TGFB1, TGFBR1, Endothelin-1 and MMP2 in SCAD patients compared to AT-AMI. [Interpretation]: We present a novel signature of plasma miRNAs in patients with SCAD. miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p discriminate SCAD from AT-AMI patients and also shed light on the pathological mechanisms underlying this condition. [Funding]: Spanish Ministry of Economy and Competitiveness (MINECO): Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV). F
- Published
- 2021
29. The DC-SIGN–related lectin LSECtin mediates antigen capture and pathogen binding by human myeloid cells
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Dominguez-Soto, Angeles, Aragoneses-Fenoll, Laura, Martin-Gayo, Enrique, Martinez-Prats, Lorena, Colmenares, Maria, Naranjo-Gomez, Marisa, Borras, Francesc E., Munoz, Pilar, Zubiaur, Mercedes, Toribio, Maria L., Delgado, Rafael, and Corbi, Angel L.
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- 2007
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30. Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID‐19 patients
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Marcos‐Jiménez, Ana, primary, Sánchez‐Alonso, Santiago, additional, Alcaraz‐Serna, Ana, additional, Esparcia, Laura, additional, López‐Sanz, Celia, additional, Sampedro‐Núñez, Miguel, additional, Mateu‐Albero, Tamara, additional, Sánchez‐Cerrillo, Ildefonso, additional, Martínez‐Fleta, Pedro, additional, Gabrie, Ligia, additional, Campo Guerola, Luciana, additional, Rodríguez‐Frade, José Miguel, additional, Casasnovas, José M., additional, Reyburn, Hugh T., additional, Valés‐Gómez, Mar, additional, López‐Trascasa, Margarita, additional, Martín‐Gayo, Enrique, additional, Calzada, María José, additional, Castañeda, Santos, additional, Fuente, Hortensia, additional, González‐Álvaro, Isidoro, additional, Sánchez‐Madrid, Francisco, additional, Muñoz‐Calleja, Cecilia, additional, and Alfranca, Arantzazu, additional
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- 2021
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31. IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study
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Galván-Román, José María, primary, Rodríguez-García, Sebastián C., additional, Roy-Vallejo, Emilia, additional, Marcos-Jiménez, Ana, additional, Sánchez-Alonso, Santiago, additional, Fernández-Díaz, Carlos, additional, Alcaraz-Serna, Ana, additional, Mateu-Albero, Tamara, additional, Rodríguez-Cortes, Pablo, additional, Sánchez-Cerrillo, Ildefonso, additional, Esparcia, Laura, additional, Martínez-Fleta, Pedro, additional, López-Sanz, Celia, additional, Gabrie, Ligia, additional, del Campo Guerola, Luciana, additional, Suárez-Fernández, Carmen, additional, Ancochea, Julio, additional, Canabal, Alfonso, additional, Albert, Patricia, additional, Rodríguez-Serrano, Diego A., additional, Aguilar, Juan Mariano, additional, del Arco, Carmen, additional, de los Santos, Ignacio, additional, García-Fraile, Lucio, additional, de la Cámara, Rafael, additional, Serra, José María, additional, Ramírez, Esther, additional, Alonso, Tamara, additional, Landete, Pedro, additional, Soriano, Joan B., additional, Martín-Gayo, Enrique, additional, Fraile Torres, Arturo, additional, Zurita Cruz, Nelly Daniela, additional, García-Vicuña, Rosario, additional, Cardeñoso, Laura, additional, Sánchez-Madrid, Francisco, additional, Alfranca, Arantzazu, additional, Muñoz-Calleja, Cecilia, additional, González-Álvaro, Isidoro, additional, Alvarado, Teresa, additional, Martínez, Pablo, additional, Javier de la Cuerda Llorente, Francisco, additional, Arco, Carmen del, additional, Villalba, Natalia, additional, Negro, Mónica, additional, Contreras, Elvira, additional, Rey, Ana del, additional, Santiago, Cristina, additional, Junquera, Manuel, additional, Caminero, Raquel, additional, Val, Francisco Javier, additional, González, Sonia, additional, Caño, Marta, additional, López, Isabel, additional, von Wernitz, Andrés, additional, Retana, Bárbara, additional, Guerra, Iñigo, additional, Sorando, Jorge, additional, Chao, Lydia, additional, Cárdenas, María José, additional, Espiga, Verónica, additional, Chicharro, Pablo, additional, Rodríguez, Pedro, additional, Alday, Iñigo Hernando, additional, Sampedro, Miguel, additional, Prada, Jorge, additional, Aldama, Eukene Rojo, additional, Real, Yolanda, additional, Caldas, María, additional, Casabona, Sergio, additional, Lanas-Gimeno, Aitor, additional, Camara, Rafael de la, additional, Alvárez, Angela Figuera, additional, Aguadol, Beatriz, additional, Morell, Alberto, additional, Zurriaga, Amparo Ibáñez, additional, Abanades, María Pérez, additional, García, Silvia Ruiz, additional, Aranda, Tomás Gallego, additional, Ruiz, María, additional, Nieto, Concepción Martínez, additional, Aspa, Javier, additional, Guerola, Luciana del Campo, additional, Fernández, Elena, additional, Calzada, Ma José, additional, Tejedor, Reyes, additional, Iglesias, Judit, additional, Suarez, Fernando, additional, Sánchez, Juan Antonio, additional, Abad, Beatriz, additional, Suarez, Carmen, additional, Santos, Ignacio de los, additional, Galván-Román, José María, additional, Roy, Emilia, additional, Sanz, Jesus, additional, Sanchez, Eduardo, additional, Moldenhauer, Fernando, additional, Casado, Pedro, additional, Curbelo, Jose, additional, Gutierrez, Angela, additional, Bautista, Azucena, additional, Giménez, Nuria Ruiz, additional, Fernandez, Angelica, additional, Parra, Pedro, additional, Moyano, Berta, additional, Barrios, Ana, additional, Real de Asua, Diego, additional, Sanchez, Beatriz, additional, Saez, Carmen, additional, Ciudad, Marianela, additional, Navas, Desiré, additional, Domingo, Laura Cardeñoso, additional, Torresano, María del Carmen Cuevas, additional, García, Diego Domingo, additional, Cavero, Teresa Alarcón, additional, Blanco, Alicia García, additional, Ramírez, Alexandra Martín, additional, Semiglia Chong, María Auxiliadora, additional, Cobos, Ainhoa Gutiérrez, additional, Fraile Torres, Arturo Manuel, additional, Sanchez-Gonzalez, Carmen, additional, Perpén, Antonio Fernádez, additional, Pérez, Carolina Díaz, additional, Soriano, Joan, additional, Cisneros, Carolina, additional, Castillo, Elena García, additional, García Pérez, Francisco Javier, additional, Girón, Rosa María, additional, Marcos, Celeste, additional, Zamora, Enrique, additional, García, Patricia García, additional, Castañeda, Santos, additional, Rodríguez-García, Sebastián, additional, Cubas, Irene Llorente, additional, Tomero, Eva G., additional, Castañeda, Noelia García, additional, Ortiz, Ana Ma, additional, Valero, Cristina, additional, Uriarte, Miren, additional, and Montes, Nuria, additional
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- 2021
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32. COVID-19 severity associates with pulmonary redistribution of CD1c+ DCs and inflammatory transitional and nonclassical monocytes
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Sánchez-Cerrillo, Ildefonso, primary, Landete, Pedro, additional, Aldave, Beatriz, additional, Sánchez-Alonso, Santiago, additional, Sánchez-Azofra, Ana, additional, Marcos-Jiménez, Ana, additional, Ávalos, Elena, additional, Alcaraz-Serna, Ana, additional, de los Santos, Ignacio, additional, Mateu-Albero, Tamara, additional, Esparcia, Laura, additional, López-Sanz, Celia, additional, Martínez-Fleta, Pedro, additional, Gabrie, Ligia, additional, del Campo Guerola, Luciana, additional, de la Fuente, Hortensia, additional, Calzada, María J., additional, González-Álvaro, Isidoro, additional, Alfranca, Arantzazu, additional, Sánchez-Madrid, Francisco, additional, Muñoz-Calleja, Cecilia, additional, Soriano, Joan B., additional, Ancochea, Julio, additional, and Martín-Gayo, Enrique, additional
- Published
- 2020
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33. Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19
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Marcos-Jiménez, Ana, primary, Sánchez-Alonso, Santiago, additional, Alcaraz-Serna, Ana, additional, Esparcia, Laura, additional, López-Sanz, Celia, additional, Sampedro-Núñez, Miguel, additional, Mateu-Albero, Tamara, additional, Sánchez-Cerrillo, Ildefonso, additional, Martínez-Fleta, Pedro, additional, Gabrie, Ligia, additional, del Campo Guerola, Luciana, additional, López-Trascasa, Margarita, additional, Martín-Gayo, Enrique, additional, Calzada, María, additional, Castañeda, Santos, additional, de la Fuente, Hortensia, additional, González-Álvaro, Isidoro, additional, Sánchez-Madrid, Francisco, additional, Muñoz-Calleja, Cecilia, additional, and Alfranca, Arantzazu, additional
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- 2020
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34. Differential Redistribution of Activated Monocyte and Dendritic Cell Subsets to the Lung Associates with Severity of COVID-19
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Sánchez-Cerrillo, Ildefonso, primary, Landete, Pedro, additional, Aldave, Beatriz, additional, Sánchez-Alonso, Santiago, additional, Azofra, Ana Sánchez, additional, Marcos-Jiménez, Ana, additional, Ávalos, Elena, additional, Alcaraz-Serna, Ana, additional, de los Santos, Ignacio, additional, Mateu-Albero, Tamara, additional, Esparcia, Laura, additional, López-Sanz, Celia, additional, Martínez-Fleta, Pedro, additional, Gabrie, Ligia, additional, del Campo Guerola, Luciana, additional, Calzada, María José, additional, González-Álvaro, Isidoro, additional, Alfranca, Arantzazu, additional, Sánchez-Madrid, Francisco, additional, Muñoz-Calleja, Cecilia, additional, Soriano, Joan B, additional, Ancochea, Julio, additional, and Martín-Gayo, Enrique, additional
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- 2020
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35. Poly I:C and STING agonist‐primed DC increase lymphoid tissue polyfunctional HIV‐1‐specific CD8+ T cells and limit CD4+ T‐cell loss in BLT mice.
- Author
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Calvet‐Mirabent, Marta, Claiborne, Daniel T., Deruaz, Maud, Tanno, Serah, Serra, Carla, Delgado‐Arévalo, Cristina, Sánchez‐Cerrillo, Ildefonso, de los Santos, Ignacio, Sanz, Jesús, García‐Fraile, Lucio, Sánchez‐Madrid, Francisco, Alfranca, Arantzazu, Muñoz‐Fernández, María Ángeles, Allen, Todd M., Buzón, Maria J., Balazs, Alejandro, Vrbanac, Vladimir, and Martín‐Gayo, Enrique
- Subjects
T cells ,LYMPHOID tissue ,CD8 antigen ,INFECTION control ,MICE - Abstract
Effective function of CD8+ T cells and enhanced innate activation of DCs in response to HIV‐1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK‐binding Kinase 1 (TBK1) might be useful to acquire controller‐like properties. Here, we evaluated the impact of the combination of 2´3´‐c´diAM(PS)2 and Poly I:C as potential adjuvants capable of potentiating DC´s abilities to induce polyfunctional HIV‐1 specific CD8+ T‐cell responses in vitro and in vivo using a humanized BLT mouse model. Adjuvant combination enhanced TBK‐1 phosphorylation and IL‐12 and IFN‐β expression on DC and increased their ability to activate polyfunctional HIV‐1‐specific CD8+ T cells in vitro. Moreover, higher proportions of hBLT mice vaccinated with ADJ‐DC exhibited less severe CD4+ T‐cell depletion following HIV‐1 infection compared to control groups. This was associated with infiltration of CD8+ T cells in the white pulp from the spleen, reduced spread of infected p24+ cells to LN, and with preserved abilities of CD8+ T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, priming of DC with PolyI:C and STING agonists might be useful for future HIV‐1 vaccine studies. [ABSTRACT FROM AUTHOR]
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- 2022
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36. Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID‐19 patients
- Author
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Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación la Caixa, European Commission, Comunidad de Madrid, Marcos Jiménez, Ana, Sánchez‐Alonso, Santiago, Alcaraz‐Serna, Ana, Esparcia-Pinedo, Laura, López‐Sanz, Celia, Sampedro-Nuñez, Miguel, Mateu‐Albero, Tamara, Sánchez‐Cerrillo, Ildefonso, Martínez‐Fleta, Petra, Gabrie, Ligia, Campo Guerola, Luciana del, Rodríguez-Frade, José Miguel, Casasnovas, José María, Reyburn, H. T., Valés-Gómez, Mar, López Trascasa, Margarita, Martín‐Gayo, Enrique, Calzada, María José, Castañeda, Santos, Fuente, Hortensia de la, González-Álvaro, Isidoro, Sánchez‐Madrid, Francisco, Muñoz‐Calleja, Cecilia, Alfranca, Arántzazu, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación la Caixa, European Commission, Comunidad de Madrid, Marcos Jiménez, Ana, Sánchez‐Alonso, Santiago, Alcaraz‐Serna, Ana, Esparcia-Pinedo, Laura, López‐Sanz, Celia, Sampedro-Nuñez, Miguel, Mateu‐Albero, Tamara, Sánchez‐Cerrillo, Ildefonso, Martínez‐Fleta, Petra, Gabrie, Ligia, Campo Guerola, Luciana del, Rodríguez-Frade, José Miguel, Casasnovas, José María, Reyburn, H. T., Valés-Gómez, Mar, López Trascasa, Margarita, Martín‐Gayo, Enrique, Calzada, María José, Castañeda, Santos, Fuente, Hortensia de la, González-Álvaro, Isidoro, Sánchez‐Madrid, Francisco, Muñoz‐Calleja, Cecilia, and Alfranca, Arántzazu
- Abstract
SARS‐CoV‐2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID‐19. We investigated whether the specific immune responses in the peripheral blood of 276 patients associated to severity and progression of COVID‐19. At admission, dramatic lymphopenia of T, B and NK cells associated to severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56‐CD16+ NK‐cells increased. Regarding humoral immunity, levels of IgM, IgA and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID‐19 patients, associating severity with an imbalanced humoral response and identifying new targets for therapeutic intervention.
- Published
- 2020
37. Spatially restricted JAG1-Notch signaling in human thymus provides suitable DC developmental niches
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Martín-Gayo, Enrique, primary, González-García, Sara, additional, García-León, María J., additional, Murcia-Ceballos, Alba, additional, Alcain, Juan, additional, García-Peydró, Marina, additional, Allende, Luis, additional, de Andrés, Belén, additional, Gaspar, María L., additional, and Toribio, María L., additional
- Published
- 2017
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38. Thymus-Derived Regulatory T Cell Development Is Regulated by C-Type Lectin-Mediated BIC/MicroRNA 155 Expression
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Sánchez-Díaz, Raquel, primary, Blanco-Dominguez, Rafael, additional, Lasarte, Sandra, additional, Tsilingiri, Katerina, additional, Martín-Gayo, Enrique, additional, Linillos-Pradillo, Beatriz, additional, de la Fuente, Hortensia, additional, Sánchez-Madrid, Francisco, additional, Nakagawa, Rinako, additional, Toribio, María L., additional, and Martín, Pilar, additional
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- 2017
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39. Effects of first-line antiretroviral therapy on the CD4/CD8 ratio and CD8 cell counts in CoRIS: a prospective multicentre cohort study
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Serrano-Villar, Sergio, Martínez-Sanz, Javier, Ron, Raquel, Talavera-Rodríguez, Alba, Fernández-Felix, Borja M, Herrera, Sabina, Muriel, Alfonso, Fanjul, Francisco, Portilla, Joaquín, Muñoz, Josefa, Amador, Concha, de Zárraga, Miguel Alberto, Vivancos, María J, Moreno, Santiago, Jarrin, Inmaculada, Moreno, Santiago, Alejos, Belén, Muñoz-Fernández, MÁngeles, Consuegra, Irene, Merino, Esperanza, García, Gema, Lirola, Ana López, García, Dácil, Asensi, Víctor, Valle, Eulalia, Rubio, Rafael, Pulido, Federico, Iribarren, José Antonio, Arrizabalaga, Julio, Gutiérrez, Félix, Masiá, Mar, Muga, Roberto, Sanvisens, Arantza, Berenguer, Juan, Vidal, Francesc, Montero, Marta, Blanco, José Ramón, López Bernarlo de Quirós, Juan Carlos, González-Garcia, Juan, Peraire, Joaquín, Arazo, Piedad, López-Aldeguer, José, Dalmau, David, Arnalich, Francisco, Rivero, Maria, Oteo, José Antonio, Sampériz, Gloria, Amengual, María José, Jaén, Angels, de los Santos, Ignacio, Repáraz, Jesús, Navarro, Gemma, Bernal, Enrique, Sanz, Jesús, Viciana, Pompeyo, García, Federico, Casado, José Luis, Del Romero, Jorge, Cano, Alfredo, Antela, Antonio, Quero, José Hernández, Riera, Melchor, Raposo, Montserrat, Santos, Jesús, Losada, Elena, Daniel, Podzamczer, Peñaranda, María, Ayerbe, Cristina Gómez, Espinosa, Nuria, Olalla, Julián, Imaz, Arkaitz, Martínez, Onofre, Curran, Adrian, Castro, Ángeles, Pérez Stachowski, Javier, Muñoz, Josefa, Vera, Francisco Jesús, Galera, Carlos, Pernas, Berta, Amador, Concha, Zuriñe, Miren, Albendin, Helena, Suárez-García, Inés, Pasquau, Francisco, Omar, Mohamed, Malmierca, Eduardo, de Zarraga, Miguel Alberto, Gómez Vidal, María Amparo, Estrada, Vicente, Górgolas, Miguel, Sanz, José, Téllez, María Jesús, Galindo, María José, Cabello, Alfonso, Rivero, Antonio, Arranz, Alberto, Cervero, Miguel, Vilalta, Ramón, Pineda, Juan A, Rivero-Juárez, Antonio, Torres, Rafael, Poveda, Eva, Rincón, Pilar, Pérez, Alexandre, Moreno, Cristina, Portilla, Irene, Díaz-Flores, Felicitas, Rivas, María E, Bisbal, Otilia, Aramburu, María J, Padilla, Sergio, Fuster, Daniel, Gutiérrez, Isabel, Viladés, Consuelo, Blanes, Marino, Arribas, José Ramón, Ibarra, Valvanera, Sanmartí, Montse, de Alda, María Ruiz, Cervantes, Manel, Salas, Ana, Dronda, Fernando, Alcaraz, Antonia, Muñoz, Leopoldo, Rodríguez, Carmen, Ribas, María Angels, Viciana, Isabel, López-Cortés, Luis, Tiraboschi, Juan, del Arco, Alfonso, Martínez, Lorena, Mena, Álvaro, Mirena, Josu, Pérez, Aurora, Ena, Javier, González-Ruano, Patricia, Vergas, Jorge, Álvarez, Beatriz, Hernández, Cristina, Ferrer, Ana, López, Pedro, Macías, Juan, Crespo, Manuel, Navarro, Maria Luisa, Iniesta, Carlos, Agea, Iván, Gómez, Juan Luis, Suárez-Zarracina, Tomás, Hernando, Asunción, Camino, Xabier, Robledano, Catalina, Ramírez, Margarita, Veloso, Sergio, Tasias, María, Bernardino, Jose Ignacio, Metola, Luis, Cairó, Mireia, de León Cano, María Teresa, Calzado, Sonia, Sarria, Cristina, Moreno, Ana, Bravo, Joaquín, Alvarez, Marta, Puerta, Teresa, Campins, Antoni A, Palacios, Rosario, Silva, Ana, de la Torre, Javier, García, Josefina, Ibarra, Sofía, Iborra, Asunción, Benito, Concha, Martín, Dolores, Pérez-Somarriba, Juncal, Prieto, Laura, Novella, María, Machuca, Isabel, Merchante, Nicolás, Morano, Luis, González, Maria Isabel, García, Luis NM, Portilla, Joaquín, Alonso, María del Mar, Pérez, Laura, Domínguez, Lourdes, Rodríguez-Arrondo, Francisco, Colomé, Joan Gregori, Padilla, Belén, Vargas, Montserrat, Castro, Iván, Castro, Juan Miguel, Sanz, Mercedes, Martinez-Lacasa, Javier, Pierola, Beatriz, Navarro, Marta, Garcia-Fraile, Lucio, Pérez-Elias, Maria Jesús, Muñoz, Ángeles, Chueca, Natalia, Carrió, Juan Carlos, Vidal, Carmen, Pérez, Carmen, Saumoy, María, Prada, José Luis, Alcaraz, Begoña, Ferrero, Oscar, Moreno, Antonio, Fenoll, Vicenta, Ruiz, Mª Pilar, Frias, Mario, Real, Luis Miguel, Miralles, Celia, Garcia, Federico, Sanz, Nieves, Sánchez-Payá, José, Pelazas, Ricardo, Rial, David, von Wichman, Miguel Ángel, Adsuar, Araceli, Gijón, Paloma, Olona, Montserrat, Calabuig, Eva, Delgado, Ana, Pérez-Martínez, Laura, Velli, Pablo, Martín-Gayo, Enrique, Gutiérrez, Carolina, Alcaraz, Maria José, Vinuesa, David, Vera, Mar, Fanjul, Francisco, Gonzalez-Domenec, Carmen, Prieto, Paula, de las Lomas, José N García, Jimeno, Amaya, López, Josefina, Merlos, Maria, Gil, Concepción, Camacho, Angela, Corma, Anais, Ocampo, Antonio, Rava, Marta, Rodríguez, Juan Carlos, Hernández, Jehovana, Bermejo, Laura, Pascual, Lidia, Pascual, Rafael, Aldamiz-Echevarría, Teresa, Rull, Anna, Cuéllar, Sandra, Escosa, Luis, Font, Roser, Madrid, Nadia, del Carmen Villalba, Maria, Martinez-Montes, Clara, Ballesteros, Juan, Murillas, Javier, Cámara, María Mar, Vidal, Asunción, Algado, José Tomas, Fernández, Marta, Pousada, Guillermo, Iribarren, Jose Antonio, Gimeno, Lina, Alemán, María Remedios, Santacreu, Mireia, Goenaga, Miguel Ángel, Tejerina, Francisco, Rodríguez-Gallego, Esther, Salavert, Miguel, Herranz, Pedro, Martinez, Marina, del Campo, Santos, Guerrero, Carlos, Ayerdi, Oskar, Homar, Francisco, de la Peña, Mireia, Meca, Marisa, Díez, Marcos, Azkune, Harkaitz, Barber, Xavier, Balsalobre, Pascual, Castellanos, Alfonso Javier, García-Bujalance, Silvia, Vivancos, Maria Jesús, Fuentes, Ana, Martin, Maria Luisa, Lopez, Iñigo, Vilchez, Helem, Lopez, Miriam, Carreres, Melissa, Ibarguren, Maialen, Agullo, Vanessa, Diez, Cristina, López-Dupla, Miguel, García, Milagros, Umerez, Maitane, Martínez-Sanz, Javier, Payeras, Antoni, Reus, Sergio, Lizardi, Aitziber, Garcia, Javier, Pérez, Leire, González-Baeza, Alicia, Anxa, Usua, González, Juan, Boix, Vicente, Kortajarena, Xabier, Pascual, Reyes, Fanciulli, Chiara, Martín-Carbonero, Maria Luz, Mellado, Maria José, Micán, Rafael, Montejano, Rocio, Montes, María Luisa, Moreno, Victoria, Pérez-Valero, Ignacio, Rúa, Guadalupe, Rodés, Berta, Sainz, Talia, Sendagorta, Elena, Stella, Natalia, Valencia, Eulalia, Velasco, Tamara, Muñoz-Fernández, María Ángeles, Torrús, Diego, Carmona, María Pilar, Roca, María, Mayoral, Mario, and Vallejo, Alejandro
- Abstract
A low CD4/CD8 ratio during antiretroviral therapy (ART) identifies people with heightened immunosenescence and increased risk of mortality. We aimed to assess the effects of integrase strand transfer inhibitor (INSTI)-based, protease inhibitor-based, or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART on long-term CD4/CD8 ratio recovery.
- Published
- 2020
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40. Spatially restricted JAG1-Notch signaling in human thymus provides suitable DC developmental niches
- Author
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Fundación Ramón Areces, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Martín-Gayo, Enrique, González-García, Sara, García-León, María J., Murcia-Ceballos, Alba, Alcaín, Juan, García-Peydró, Marina, Allende, Luis, Andrés, Begoña, Gaspar, María Luisa, Toribio, María Luisa, Fundación Ramón Areces, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Martín-Gayo, Enrique, González-García, Sara, García-León, María J., Murcia-Ceballos, Alba, Alcaín, Juan, García-Peydró, Marina, Allende, Luis, Andrés, Begoña, Gaspar, María Luisa, and Toribio, María Luisa
- Abstract
A key unsolved question regarding the developmental origin of conventional and plasmacytoid dendritic cells (cDCs and pDCs, respectively) resident in the steady-state thymus is whether early thymic progenitors (ETPs) could escape T cell fate constraints imposed normally by a Notch-inductive microenvironment and undergo DC development. By modeling DC generation in bulk and clonal cultures, we show here that Jagged1 (JAG1)-mediated Notch signaling allows human ETPs to undertake a myeloid transcriptional program, resulting in GATA2-dependent generation of CD34 CD123 progenitors with restricted pDC, cDC, and monocyte potential, whereas Delta-like1 signaling down-regulates GATA2 and impairs myeloid development. Progressive commitment to the DC lineage also occurs intrathymically, as myeloid-primed CD123 monocyte/DC and common DC progenitors, equivalent to those previously identified in the bone marrow, are resident in the normal human thymus. The identification of a discrete JAG1 thymic medullary niche enriched for DC-lineage cells expressing Notch receptors further validates the human thymus as a DC-poietic organ, which provides selective microenvironments permissive for DC development.
- Published
- 2017
41. Función tolorógina, origen y diferenciación de las células dendríticas plasmacitoides residentes en el timo humano
- Author
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Martín Gayo, Enrique, Toribio García, María Luisa, and Universidad Autónoma de Madrid. Departamento de Biología Molecular
- Subjects
Timo - Tesis doctorales - Abstract
Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 17-12-2010
- Published
- 2010
42. Intravenous Immunoglobulin Promotes Antitumor Responses by Modulating Macrophage Polarization
- Author
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Domínguez-Soto, Angeles, primary, de las Casas-Engel, Mateo, additional, Bragado, Rafael, additional, Medina-Echeverz, José, additional, Aragoneses-Fenoll, Laura, additional, Martín-Gayo, Enrique, additional, van Rooijen, Nico, additional, Berraondo, Pedro, additional, Toribio, María L., additional, Moro, María A., additional, Cuartero, Isabel, additional, Castrillo, Antonio, additional, Sancho, David, additional, Sánchez-Torres, Carmen, additional, Bruhns, Pierre, additional, Sánchez-Ramón, Silvia, additional, and Corbí, Angel L., additional
- Published
- 2014
- Full Text
- View/download PDF
43. The novel RUNX3/p33 isoform is induced upon monocyte-derived dendritic cell maturation and downregulates IL-8 expression
- Author
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Ministerio de Educación y Ciencia (España), Ministerio de Sanidad y Consumo (España), Instituto de Salud Carlos III, Fundación para la Investigación y la Prevención del Sida en España, Fundación Mutua Madrileña, Puig-Kröger, Amaya, Aguilera-Montilla, Noemí, Martínez-Nuñez, Rocío T., Domínguez-Soto, Ángeles, Sánchez-Cabo, Fátima, Martín-Gayo, Enrique, Zaballos, Ángel, Toribio, María Luisa, Groner, Yoram, Ito, Yoshiaki, Dopazo, Ana, Corcuera, María Teresa, Alonso Martín, María J., Vega Palacios, Miguel A., Corbí, Angel L., Ministerio de Educación y Ciencia (España), Ministerio de Sanidad y Consumo (España), Instituto de Salud Carlos III, Fundación para la Investigación y la Prevención del Sida en España, Fundación Mutua Madrileña, Puig-Kröger, Amaya, Aguilera-Montilla, Noemí, Martínez-Nuñez, Rocío T., Domínguez-Soto, Ángeles, Sánchez-Cabo, Fátima, Martín-Gayo, Enrique, Zaballos, Ángel, Toribio, María Luisa, Groner, Yoram, Ito, Yoshiaki, Dopazo, Ana, Corcuera, María Teresa, Alonso Martín, María J., Vega Palacios, Miguel A., and Corbí, Angel L.
- Abstract
RUNX proteins are heterodimeric factors that play crucial roles during development and differentiation of cells of the immune system. The RUNX3 transcription factor controls lineage decisions during thymopoiesis and T-cell differentiation, and modulates myeloid cell effector functions. We now report the characterization of the human RUNX3/p33 isoform, generated by splicing out a Runt DNA-binding domain-encoding exon, and whose transcriptional activities differ from those of the prototypic RUNX3/p44 molecule. Unlike RUNX3/p44, RUNX3/p33 is induced upon maturation of monocyte-derived dendritic cells (MDDC), and is unable to transactivate the regulatory regions of the CD11a, CD11c and CD49e integrin genes. Overexpression of RUNX3/p33 in myeloid cell lines led to diminished expression of genes involved in inflammatory responses. Moreover, overexpression of RUNX3/p33 down-modulated the basal level of IL-8 production from immature monocyte-derived dendritic cells (MDDC). Besides, siRNA-mediated knock-down of RUNX3 led to diminished levels of IL-8 RNA in immature MDDC, and modulated the neutrophil-recruiting capacity of myeloid cell line supernatants. Since IL-8 promotes neutrophil chemotaxis and degranulation during inflammatory responses, and exerts mitogenic and angiogenic actions within tumor microenvironment, our results imply that myeloid RUNX3 expression regulates the recruitment of leukocytes towards inflammatory foci and might also contribute to human cancer progression.
- Published
- 2010
44. CSL–MAML-dependent Notch1 signaling controls T lineage–specific IL-7R gene expression in early human thymopoiesis and leukemia
- Author
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Comunidad de Madrid, Fundación la Caixa, Fundación Mutua Madrileña, Instituto de Salud Carlos III, Fundación Ramón Areces, Ministerio de Ciencia e Innovación (España), European Commission, González-García, Sara, García-Peydró, Marina, Martín-Gayo, Enrique, Ballestar, Estéban, Esteller, Manel, Bornstein, Rafael, Pompa, José Luis de la, Ferrando, Adolfo, Toribio, María Luisa, Comunidad de Madrid, Fundación la Caixa, Fundación Mutua Madrileña, Instituto de Salud Carlos III, Fundación Ramón Areces, Ministerio de Ciencia e Innovación (España), European Commission, González-García, Sara, García-Peydró, Marina, Martín-Gayo, Enrique, Ballestar, Estéban, Esteller, Manel, Bornstein, Rafael, Pompa, José Luis de la, Ferrando, Adolfo, and Toribio, María Luisa
- Abstract
Notch1 activation is essential for T-lineage specification of lymphomyeloid progenitors seeding the thymus. Progression along the T cell lineage further requires cooperative signaling provided by the interleukin 7 receptor (IL-7R), but the molecular mechanisms responsible for the dynamic and lineage-specific regulation of IL-7R during thymopoiesis are unknown. We show that active Notch1 binds to a conserved CSL-binding site in the human IL7R gene promoter and critically regulates IL7R transcription and IL-7R chain (IL-7R) expression via the CSL–MAML complex. Defective Notch1 signaling selectively impaired IL-7R expression in T-lineage cells, but not B-lineage cells, and resulted in a compromised expansion of early human developing thymocytes, which was rescued upon ectopic IL-7R expression. The pathological implications of these findings are demonstrated by the regulation of IL-7R expression downstream of Notch1 in T cell leukemias. Thus, Notch1 controls early T cell development, in part by regulating the stage- and lineage-specific expression of IL-7R.
- Published
- 2009
45. CSL–MAML-dependent Notch1 signaling controls T lineage–specific IL-7Rα gene expression in early human thymopoiesis and leukemia
- Author
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González-García, Sara, primary, García-Peydró, Marina, additional, Martín-Gayo, Enrique, additional, Ballestar, Esteban, additional, Esteller, Manel, additional, Bornstein, Rafael, additional, de la Pompa, José Luis, additional, Ferrando, Adolfo A., additional, and Toribio, María L., additional
- Published
- 2009
- Full Text
- View/download PDF
46. A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers
- Author
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Martin-Gayo, Enrique, Cole, Michael B., Kolb, Kellie E., Ouyang, Zhengyu, Cronin, Jacqueline, Kazer, Samuel W., Ordovas-Montanes, Jose, Lichterfeld, Mathias, Walker, Bruce D., Yosef, Nir, Shalek, Alex K., and Yu, Xu G.
- Subjects
HIV-1 ,Dendritic cell ,Single-cell RNA-seq ,Single-cell genomics ,Elite controller ,Adjuvant ,Reproducibility ,Differential expression - Abstract
Background: Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-sequencing to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. Results: To overcome the potentially confounding effects of donor-to-donor variability, we present a generally applicable computational framework for identifying reproducible patterns in gene expression across donors who share a unifying classification. Applying it, we discover a highly functional antiviral DC state in ECs whose fractional abundance after in vitro exposure to HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and that effectively primes polyfunctional T cell responses in vitro. By integrating information from existing genomic databases into our reproducibility-based analysis, we identify and validate select immunomodulators that increase the fractional abundance of this state in primary peripheral blood mononuclear cells from healthy individuals in vitro. Conclusions: Overall, our results demonstrate how single-cell approaches can reveal previously unappreciated, yet important, immune behaviors and empower rational frameworks for modulating systems-level immune responses that may prove therapeutically and prophylactically useful. Electronic supplementary material The online version of this article (10.1186/s13059-017-1385-x) contains supplementary material, which is available to authorized users.
- Published
- 2018
- Full Text
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47. Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers
- Author
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Martin-Gayo, Enrique, Buzon, Maria Jose, Ouyang, Zhengyu, Hickman, Taylor, Cronin, Jacqueline, Pimenova, Dina, Walker, Bruce D., Lichterfeld, Mathias, and Yu, Xu G.
- Abstract
The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes.
- Published
- 2015
- Full Text
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48. HIV-1 persistence in CD4+ T cells with stem cell-like properties
- Author
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Buzon, Maria J., Sun, Hong, Li, Chun, Shaw, Amy, Seiss, Katherine, Ouyang, Zhengyu, Martin-Gayo, Enrique, Leng, Jin, Henrich, Timothy J., Li, Jonathan Z., Pereyra, Florencia, Zurakowski, Ryan, Walker, Bruce D., Rosenberg, Eric S., Yu, Xu G., and Lichterfeld, Mathias
- Abstract
Cellular HIV-1 reservoirs that persist despite antiretroviral treatment are incompletely defined. We show that during suppressive antiretroviral therapy, CD4+ T memory stem cells (TSCM) harbor high per-cell levels of HIV-1 DNA, and make increasing contributions to the total viral CD4+ T cell reservoir over time. Moreover, phylogenetic studies suggested long-term persistence of viral quasispecies in CD4+ TSCM cells. Thus, HIV-1 may exploit stem cell characteristics of cellular immune memory to promote long-term viral persistence.
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- 2014
- Full Text
- View/download PDF
49. LILRB2 Interaction with HLA Class I Correlates with Control of HIV-1 Infection
- Author
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Bashirova, Arman A., Martin-Gayo, Enrique, Jones, Des C., Qi, Ying, Apps, Richard, Gao, Xiaojiang, Burke, Patrick S., Taylor, Craig J., Rogich, Jerome, Wolinsky, Steven, Bream, Jay H., Duggal, Priya, Hussain, Shehnaz, Martinson, Jeremy, Weintrob, Amy, Kirk, Gregory D., Fellay, Jacques, Buchbinder, Susan P., Goedert, James J., Deeks, Steven G., Pereyra, Florencia, Trowsdale, John, Lichterfeld, Mathias, Telenti, Amalio, Walker, Bruce D., Allen, Rachel L., Carrington, Mary, and Yu, Xu G.
- Subjects
Medicine ,Infectious diseases ,Viral diseases ,HIV ,Retrovirology and HIV immunopathogenesis - Abstract
Natural progression of HIV-1 infection depends on genetic variation in the human major histocompatibility complex (MHC) class I locus, and the CD8+ T cell response is thought to be a primary mechanism of this effect. However, polymorphism within the MHC may also alter innate immune activity against human immunodeficiency virus type 1 (HIV-1) by changing interactions of human leukocyte antigen (HLA) class I molecules with leukocyte immunoglobulin-like receptors (LILR), a group of immunoregulatory receptors mainly expressed on myelomonocytic cells including dendritic cells (DCs). We used previously characterized HLA allotype-specific binding capacities of LILRB1 and LILRB2 as well as data from a large cohort of HIV-1-infected individuals (N = 5126) to test whether LILR-HLA class I interactions influence viral load in HIV-1 infection. Our analyses in persons of European descent, the largest ethnic group examined, show that the effect of HLA-B alleles on HIV-1 control correlates with the binding strength between corresponding HLA-B allotypes and LILRB2 (p = 10−2). Moreover, overall binding strength of LILRB2 to classical HLA class I allotypes, defined by the HLA-A/B/C genotypes in each patient, positively associates with viral replication in the absence of therapy in patients of both European (p = 10−11–10−9) and African (p = 10−5–10−3) descent. This effect appears to be driven by variations in LILRB2 binding affinities to HLA-B and is independent of individual class I allelic effects that are not related to the LILRB2 function. Correspondingly, in vitro experiments suggest that strong LILRB2-HLA binding negatively affects antigen-presenting properties of DCs. Thus, we propose an impact of LILRB2 on HIV-1 disease outcomes through altered regulation of DCs by LILRB2-HLA engagement.
- Published
- 2014
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50. Interactions between HLA-B and Leukocyte Immunoglobulin like Receptors B2 (LILRB2) Correlate with HIV-1 Disease Outcomes
- Author
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Martin Gayo, Enrique, Jones, D., Pereyra, Florencia M., Lichterfeld, Mathias, Allen, R. L., and Yu, X. G.
- Published
- 2012
- Full Text
- View/download PDF
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