Respuesta inmunoreguladora y su relación con la inmunopatología cardiaca en la infección por Tryipanosoma cruzi

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 07-09-201

Cyclooxygenase-2 and prostaglandin E<inf>2</inf> signaling through prostaglandin receptor EP- 2 favor the development of myocarditis during acute trypanosoma cruzi infection

Inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA). Here, we have investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart. Interestingly, COX-2 was expressed by CD68+ myeloid heart-infiltrating cells. In addition, infiltrating myeloid CD11b+Ly6G- cells purified from infected heart tissue express COX-2 and produce prostaglandin E2 (PGE2) ex vivo. T. cruzi infections in COX-2 or PGE2- dependent prostaglandin receptor EP-2 deficient mice indicate that both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte infiltration and to the release of chemokines and inflammatory cytokines in the heart of T. cruzi infected mice. In conclusion, COX-2 plays a detrimental role in acute Chagas disease myocarditis and points to COX-2 as a potential target for immune intervention.This work was supported by (NG) grants from “Fondo de Investigaciones Sanitarias” (PS09/00538 and PI12/00289); “Universidad Autónoma de Madrid” and “Comunidad de Madrid” (CC08-UAM/SAL-4440/08); by (MF) grants from “Ministerio de Ciencia e Innovación” (SAF2010-17833); “Red de Investigación de Centros de Enfermedades Tropicales” (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD- 2332) and “Fundación Ramón Areces”. NAG was recipient of a ISCIII Ph.D. fellowship financed by the Spanish “Ministerio de Sanidad”. CCM and HC were recipients of contracts from SAF2010-17833 and PI060388, respectively.Peer Reviewe

Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies

© 2023 García-Calderón, Sierro-Martínez, García-Guerrero, Sanoja-Flores, Muñoz-García, Ruiz-Maldonado, Jimenez-Leon, Delgado-Serrano, Molinos-Quintana, Guijarro-Albaladejo, Carrasco-Brocal, Lucena, García-Lozano, Blázquez-Goñi, Reguera-Ortega, González-Escribano, Reinoso-Segura, Briones, Pérez-Simón and Caballero-Velázquez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Purpose: CAR-T cell therapy has proven to be a disruptive treatment in the hematology field, however, less than 50% of patients maintain long-term response and early predictors of outcome are still inconsistently defined. Here, we aimed to optimize the detection of CD19 CAR-T cells in blood and to identify phenotypic features as early biomarkers associated with toxicity and outcomes.Experimental design: In this study, monitoring by flow cytometry and digital PCR (dPCR), and immunophenotypic characterization of circulating CAR-T cells from 48 patients treated with Tisa-cel or Axi-cel was performed.Results: Validation of the flow cytometry reagent for the detection of CAR-T cells in blood revealed CD19 protein conjugated with streptavidin as the optimal detection method. Kinetics of CAR-T cell expansion in blood confirmed median day of peak expansion at seven days post-infusion by both flow cytometry and digital PCR. Circulating CAR-T cells showed an activated, proliferative, and exhausted phenotype at the time of peak expansion. Patients with increased expansion showed more severe CRS and ICANs. Immunophenotypic characterization of CAR-T cells at the peak expansion identified the increased expression of co-inhibitory molecules PD1 and LAG3 and reduced levels of the cytotoxicity marker CD107a as predictors of a better long-term disease control.Conclusions: These data show the importance of CAR-T cells in vivo monitoring and identify the expression of PD1LAG3 and CD107a as early biomarkers of long-term disease control after CAR-T cell therapy.This work has been supported by the Instituto de Salud Carlos III (ISCIII), Project RD21/0017/0021, Red Española de Terapias Avanzadas TERAV funded by European Union-NextGenerationEU. “Plan de Recuperación Transformación y Resiliencia” and Consejería de Salud y Familia, Junta de Andalucía PECART-0185-2020-7, PECART-0185-2020 CSYF 2021 – Proyectos Fondos FEDER. Proyectos estratégicos en Investigación en CAR-T. “Monitorización inmune tras tratamiento con células CAR-T: búsqueda de biomarcadores y medición de la actividadmetabólica como predictores de respuesta”.Peer reviewe

Taking the pulse of Earth's tropical forests using networks of highly distributed plots

Tropical forests are the most diverse and productive ecosystems on Earth. While better understanding of these forests is critical for our collective future, until quite recently efforts to measure and monitor them have been largely disconnected. Networking is essential to discover the answers to questions that transcend borders and the horizons of funding agencies. Here we show how a global community is responding to the challenges of tropical ecosystem research with diverse teams measuring forests tree-by-tree in thousands of long-term plots. We review the major scientific discoveries of this work and show how this process is changing tropical forest science. Our core approach involves linking long-term grassroots initiatives with standardized protocols and data management to generate robust scaled-up results. By connecting tropical researchers and elevating their status, our Social Research Network model recognises the key role of the data originator in scientific discovery. Conceived in 1999 with RAINFOR (South America), our permanent plot networks have been adapted to Africa (AfriTRON) and Southeast Asia (T-FORCES) and widely emulated worldwide. Now these multiple initiatives are integrated via ForestPlots.net cyber-infrastructure, linking colleagues from 54 countries across 24 plot networks. Collectively these are transforming understanding of tropical forests and their biospheric role. Together we have discovered how, where and why forest carbon and biodiversity are responding to climate change, and how they feedback on it. This long-term pan-tropical collaboration has revealed a large long-term carbon sink and its trends, as well as making clear which drivers are most important, which forest processes are affected, where they are changing, what the lags are, and the likely future responses of tropical forests as the climate continues to change. By leveraging a remarkably old technology, plot networks are sparking a very modern revolution in tropical forest science. In the future, humanity can benefit greatly by nurturing the grassroots communities now collectively capable of generating unique, long-term understanding of Earth's most precious forests.Additional co-authors: Susan Laurance, William Laurance, Francoise Yoko Ishida, Andrew Marshall, Catherine Waite, Hannsjoerg Woell, Jean-Francois Bastin, Marijn Bauters, Hans Beeckman, Pfascal Boeckx, Jan Bogaert, Charles De Canniere, Thales de Haulleville, Jean-Louis Doucet, Olivier Hardy, Wannes Hubau, Elizabeth Kearsley, Hans Verbeeck, Jason Vleminckx, Steven W. Brewer, Alfredo Alarcón, Alejandro Araujo-Murakami, Eric Arets, Luzmila Arroyo, Ezequiel Chavez, Todd Fredericksen, René Guillén Villaroel, Gloria Gutierrez Sibauty, Timothy Killeen, Juan Carlos Licona, John Lleigue, Casimiro Mendoza, Samaria Murakami, Alexander Parada Gutierrez, Guido Pardo, Marielos Peña-Claros, Lourens Poorter, Marisol Toledo, Jeanneth Villalobos Cayo, Laura Jessica Viscarra, Vincent Vos, Jorge Ahumada, Everton Almeida, Jarcilene Almeida, Edmar Almeida de Oliveira, Wesley Alves da Cruz, Atila Alves de Oliveira, Fabrício Alvim Carvalho, Flávio Amorim Obermuller, Ana Andrade, Fernanda Antunes Carvalho, Simone Aparecida Vieira, Ana Carla Aquino, Luiz Aragão, Ana Claudia Araújo, Marco Antonio Assis, Jose Ataliba Mantelli Aboin Gomes, Fabrício Baccaro, Plínio Barbosa de Camargo, Paulo Barni, Jorcely Barroso, Luis Carlos Bernacci, Kauane Bordin, Marcelo Brilhante de Medeiros, Igor Broggio, José Luís Camargo, Domingos Cardoso, Maria Antonia Carniello, Andre Luis Casarin Rochelle, Carolina Castilho, Antonio Alberto Jorge Farias Castro, Wendeson Castro, Sabina Cerruto Ribeiro, Flávia Costa, Rodrigo Costa de Oliveira, Italo Coutinho, John Cunha, Lola da Costa, Lucia da Costa Ferreira, Richarlly da Costa Silva, Marta da Graça Zacarias Simbine, Vitor de Andrade Kamimura, Haroldo Cavalcante de Lima, Lia de Oliveira Melo, Luciano de Queiroz, José Romualdo de Sousa Lima, Mário do Espírito Santo, Tomas Domingues, Nayane Cristina dos Santos Prestes, Steffan Eduardo Silva Carneiro, Fernando Elias, Gabriel Eliseu, Thaise Emilio, Camila Laís Farrapo, Letícia Fernandes, Gustavo Ferreira, Joice Ferreira, Leandro Ferreira, Socorro Ferreira, Marcelo Fragomeni Simon, Maria Aparecida Freitas, Queila S. García, Angelo Gilberto Manzatto, Paulo Graça, Frederico Guilherme, Eduardo Hase, Niro Higuchi, Mariana Iguatemy, Reinaldo Imbrozio Barbosa, Margarita Jaramillo, Carlos Joly, Joice Klipel, Iêda Leão do Amaral, Carolina Levis, Antonio S. Lima, Maurício Lima Dan, Aline Lopes, Herison Madeiros, William E. Magnusson, Rubens Manoel dos Santos, Beatriz Marimon, Ben Hur Marimon Junior, Roberta Marotti Martelletti Grillo, Luiz Martinelli, Simone Matias Reis, Salomão Medeiros, Milton Meira-Junior, Thiago Metzker, Paulo Morandi, Natanael Moreira do Nascimento, Magna Moura, Sandra Cristina Müller, Laszlo Nagy, Henrique Nascimento, Marcelo Nascimento, Adriano Nogueira Lima, Raimunda Oliveira de Araújo, Jhonathan Oliveira Silva, Marcelo Pansonato, Gabriel Pavan Sabino, Karla Maria Pedra de Abreu, Pablo José Francisco Pena Rodrigues, Maria Piedade, Domingos Rodrigues, José Roberto Rodrigues Pinto, Carlos Quesada, Eliana Ramos, Rafael Ramos, Priscyla Rodrigues, Thaiane Rodrigues de Sousa, Rafael Salomão, Flávia Santana, Marcos Scaranello, Rodrigo Scarton Bergamin, Juliana Schietti, Jochen Schöngart, Gustavo Schwartz, Natalino Silva, Marcos Silveira, Cristiana Simão Seixas, Marta Simbine, Ana Claudia Souza, Priscila Souza, Rodolfo Souza, Tereza Sposito, Edson Stefani Junior, Julio Daniel do Vale, Ima Célia Guimarães Vieira, Dora Villela, Marcos Vital, Haron Xaud, Katia Zanini, Charles Eugene Zartman, Nur Khalish Hafizhah Ideris, Faizah binti Hj Metali, Kamariah Abu Salim, Muhd Shahruney Saparudin, Rafizah Mat Serudin, Rahayu Sukmaria Sukri, Serge Begne, George Chuyong, Marie Noel Djuikouo, Christelle Gonmadje, Murielle Simo-Droissart, Bonaventure Sonké, Hermann Taedoumg, Lise Zemagho, Sean Thomas, Fidèle Baya, Gustavo Saiz, Javier Silva Espejo, Dexiang Chen, Alan Hamilton, Yide Li, Tushou Luo, Shukui Niu, Han Xu, Zhang Zhou, Esteban Álvarez-Dávila, Juan Carlos Andrés Escobar, Henry Arellano-Peña, Jaime Cabezas Duarte, Jhon Calderón, Lina Maria Corrales Bravo, Borish Cuadrado, Hermes Cuadros, Alvaro Duque, Luisa Fernanda Duque, Sandra Milena Espinosa, Rebeca Franke-Ante, Hernando García, Alejandro Gómez, Roy González-M., Álvaro Idárraga-Piedrahíta, Eliana Jimenez, Rubén Jurado, Wilmar López Oviedo, René López-Camacho, Omar Aurelio Melo Cruz, Irina Mendoza Polo, Edwin Paky, Karen Pérez, Angel Pijachi, Camila Pizano, Adriana Prieto, Laura Ramos, Zorayda Restrepo Correa, James Richardson, Elkin Rodríguez, Gina M. Rodriguez M., Agustín Rudas, Pablo Stevenson, Markéta Chudomelová, Martin Dancak, Radim Hédl, Stanislav Lhota, Martin Svatek, Jacques Mukinzi, Corneille Ewango, Terese Hart, Emmanuel Kasongo Yakusu, Janvier Lisingo, Jean-Remy Makana, Faustin Mbayu, Benjamin Toirambe, John Tshibamba Mukendi, Lars Kvist, Gustav Nebel, Selene Báez, Carlos Céron, Daniel M. Griffith, Juan Ernesto Guevara Andino, David Neill, Walter Palacios, Maria Cristina Peñuela-Mora, Gonzalo Rivas-Torres, Gorky Villa, Sheleme Demissie, Tadesse Gole, Techane Gonfa, Kalle Ruokolainen, Michel Baisie, Fabrice Bénédet, Wemo Betian, Vincent Bezard, Damien Bonal, Jerôme Chave, Vincent Droissart, Sylvie Gourlet-Fleury, Annette Hladik, Nicolas Labrière, Pétrus Naisso, Maxime Réjou-Méchain, Plinio Sist, Lilian Blanc, Benoit Burban, Géraldine Derroire, Aurélie Dourdain, Clement Stahl, Natacha Nssi Bengone, Eric Chezeaux, Fidèle Evouna Ondo, Vincent Medjibe, Vianet Mihindou, Lee White, Heike Culmsee, Cristabel Durán Rangel, Viviana Horna, Florian Wittmann, Stephen Adu-Bredu, Kofi Affum-Baffoe, Ernest Foli, Michael Balinga, Anand Roopsind, James Singh, Raquel Thomas, Roderick Zagt, Indu K. Murthy, Kuswata Kartawinata, Edi Mirmanto, Hari Priyadi, Ismayadi Samsoedin, Terry Sunderland, Ishak Yassir, Francesco Rovero, Barbara Vinceti, Bruno Hérault, Shin-Ichiro Aiba, Kanehiro Kitayama, Armandu Daniels, Darlington Tuagben, John T. Woods, Muhammad Fitriadi, Alexander Karolus, Kho Lip Khoon, Noreen Majalap, Colin Maycock, Reuben Nilus, Sylvester Tan, Almeida Sitoe, Indiana Coronado G., Lucas Ojo, Rafael de Assis, Axel Dalberg Poulsen, Douglas Sheil, Karen Arévalo Pezo, Hans Buttgenbach Verde, Victor Chama Moscoso, Jimmy Cesar Cordova Oroche, Fernando Cornejo Valverde, Massiel Corrales Medina, Nallaret Davila Cardozo, Jano de Rutte Corzo, Jhon del Aguila Pasquel, Gerardo Flores Llampazo, Luis Freitas, Darcy Galiano Cabrera, Roosevelt García Villacorta, Karina Garcia Cabrera, Diego García Soria, Leticia Gatica Saboya, Julio Miguel Grandez Rios, Gabriel Hidalgo Pizango, Eurídice Honorio Coronado, Isau Huamantupa-Chuquimaco, Walter Huaraca Huasco, Yuri Tomas Huillca Aedo, Jose Luis Marcelo Peña, Abel Monteagudo Mendoza, Vanesa Moreano Rodriguez, Percy Núñez Vargas, Sonia Cesarina Palacios Ramos, Nadir Pallqui Camacho, Antonio Peña Cruz, Freddy Ramirez Arevalo, José Reyna Huaymacari, Carlos Reynel Rodriguez, Marcos Antonio Ríos Paredes, Lily Rodriguez Bayona, Rocio del Pilar Rojas Gonzales, Maria Elena Rojas Peña, Norma Salinas Revilla, Yahn Carlos Soto Shareva, Raul Tupayachi Trujillo, Luis Valenzuela Gamarra, Rodolfo Vasquez Martinez, Jim Vega Arenas, Christian Amani, Suspense Averti Ifo, Yannick Bocko, Patrick Boundja, Romeo Ekoungoulou, Mireille Hockemba, Donatien Nzala, Alusine Fofanah, David Taylor, Guillermo Bañares-de Dios, Luis Cayuela, Íñigo Granzow-de la Cerda, Manuel Macía, Juliana Stropp, Maureen Playfair, Verginia Wortel, Toby Gardner, Robert Muscarella, Hari Priyadi, Ervan Rutishauser, Kuo-Jung Chao, Pantaleo Munishi, Olaf Bánki, Frans Bongers, Rene Boot, Gabriella Fredriksson, Jan Reitsma, Hans ter Steege, Tinde van Andel, Peter van de Meer, Peter van der Hout, Mark van Nieuwstadt, Bert van Ulft, Elmar Veenendaal, Ronald Vernimmen, Pieter Zuidema, Joeri Zwerts, Perpetra Akite, Robert Bitariho, Colin Chapman, Eilu Gerald, Miguel Leal, Patrick Mucunguzi, Miguel Alexiades, Timothy R. Baker, Karina Banda, Lindsay Banin, Jos Barlow, Amy Bennett, Erika Berenguer, Nicholas Berry, Neil M. Bird, George A. Blackburn, Francis Brearley, Roel Brienen, David Burslem, Lidiany Carvalho, Percival Cho, Fernanda Coelho, Murray Collins, David Coomes, Aida Cuni-Sanchez, Greta Dargie, Kyle Dexter, Mat Disney, Freddie Draper, Muying Duan, Adriane Esquivel-Muelbert, Robert Ewers, Belen Fadrique, Sophie Fauset, Ted R. Feldpausch, Filipe França, David Galbraith, Martin Gilpin, Emanuel Gloor, John Grace, Keith Hamer, David Harris, Tommaso Jucker, Michelle Kalamandeen, Bente Klitgaard, Aurora Levesley, Simon L. Lewis, Jeremy Lindsell, Gabriela Lopez-Gonzalez, Jon Lovett, Yadvinder Malhi, Toby Marthews, Emma McIntosh, Karina Melgaço, William Milliken, Edward Mitchard, Peter Moonlight, Sam Moore, Alexandra Morel, Julie Peacock, Kelvin Peh, Colin Pendry, R. Toby Pennington, Luciana de Oliveira Pereira, Carlos Peres, Oliver L. Phillips, Georgia Pickavance, Thomas Pugh, Lan Qie, Terhi Riutta, Katherine Roucoux, Casey Ryan, Tiina Sarkinen, Camila Silva Valeria, Dominick Spracklen, Suzanne Stas, Martin Sullivan, Michael Swaine, Joey Talbot, James Taplin, Geertje van der Heijden, Laura Vedovato, Simon Willcock, Mathew Williams, Luciana Alves, Patricia Alvarez Loayza, Gabriel Arellano, Cheryl Asa, Peter Ashton, Gregory Asner, Terry Brncic, Foster Brown, Robyn Burnham, Connie Clark, James Comiskey, Gabriel Damasco, Stuart Davies, Tony Di Fiore, Terry Erwin, William Farfan-Rios, Jefferson Hall, David Kenfack, Thomas Lovejoy, Roberta Martin, Olga Martha Montiel, John Pipoly, Nigel Pitman, John Poulsen, Richard Primack, Miles Silman, Marc Steininger, Varun Swamy, John Terborgh, Duncan Thomas, Peter Umunay, Maria Uriarte, Emilio Vilanova Torre, Ophelia Wang, Kenneth Young, Gerardo A. Aymard C., Lionel Hernández, Rafael Herrera Fernández, Hirma Ramírez-Angulo, Pedro Salcedo, Elio Sanoja, Julio Serrano, Armando Torres-Lezama, Tinh Cong Le, Trai Trong Le, Hieu Dang Tra

Desarrollo Psicomotor en Preescolares con Anemia Ferropenica

La anemia ferrop&eacute;nica es una patolog&iacute;a muy frecuente en la infancia, con alta prevalencia en pa&iacute;ses subdesarrollados. Se ha demostrado la relaci&oacute;n negativa entre la presencia de anemia ferropriva y el desarrollo neurol&oacute;gico en los ni&ntilde;os. El objetivo del presente estudio fue conocer el desarrollo psicomotor de los ni&ntilde;os en edad preescolar con anemia ferrop&eacute;nica. M&eacute;todos: se incluyeron 60 ni&ntilde;os con edades comprendidas entre 2 y 6 a&ntilde;os, alumnos del Preescolar Estatal San Carlos, Maracay, Estado Aragua, a los cuales se les practic&oacute; determinaci&oacute;n capilar de hemoglobina. En 30 de ellos la hemoglobina present&oacute; valores inferiores a 11 g/dL. La muestra de sangre permiti&oacute; determinar los valores hematim&eacute;tricos correspondientes a la hematolog&iacute;a completa de rutina y la concentraci&oacute;n de hierro s&eacute;rico. Resultados: 30 ni&ntilde;os presentaron anemia microc&iacute;tica con amplitud de distribuci&oacute;n eritrocitaria (RDW) elevada, y solo 4 de ellos mostraron concentraci&oacute;n de hierro s&eacute;rico bajo. De los 30 ni&ntilde;os an&eacute;micos, 17 eran de sexo masculino y 13 de sexo femenino. Estos 30 ni&ntilde;os fueron valorados con el Test de Denver para determinar el desarrollo psicomotor. Se encontr&oacute; que 63,3% de estos ni&ntilde;os obtuvo calificaci&oacute;n anormal en el Test de Denver, reflejado en la mayor&iacute;a de los casos en el &aacute;rea de lenguaje (63,3%); la actividad motora fina fue anormal en 43,3% de los ni&ntilde;os y normal en el resto de los ni&ntilde;os estudiados. Conclusiones:los resultados evidencian el efecto negativo del d&eacute;ficit de hierro en el &aacute;rea cognitiva de los ni&ntilde;os preescolares.AbstractPSICOMOTOR DEVELOPMENT IN PRESCHOOL CHILDREN WITH FERROPENIC ANEMIAIron deficiency anemia is a very common disease in childhood, with a high prevalence in developing countries. It has been shown a negative relationship between iron deficiency anemia and the neurological development of children. The objective of this study was to determine the psychomotor development of preschool children with iron deficiency anemia. Methods: We included 60 children aged 2 to 6 years old, from the Preschool institution San Carlos, Maracay, Aragua State, Venezuela. In these 60 children the capillary hemoglobin assay revealed that 30 of them had hemoglobin concentration below 11 g/dL. All preschool children underwent blood sampling to determine their hematimetric values and serum iron concentration. Results: It was found that 30 children had microcytic anemia with elevated RDW and only 4 of them showed low serum iron concentration. Children with microcitic anemia were 17 male and 13 female. These 30 children were evaluated with the Denver Test for psychomotor development screening and we found that an abnormal score was exhibited by 63.3% of them, mainly reflected in the language area (63.3%). Fine motor activity was abnormal in 43.3% and normal in 43.3% of anemic children. Conclusions: These results demonstrate a negative association between iron deficiency with cognitive deficit in preschool children

Influencia de variables ambientales sobre la presenciade Panstrongylus Geniculatus (Latreille, 1811) en domicilios del área metropolitana de Caracas, Venezuela

oai:ojs2.tesla.puertomaderoeditorial.com.ar:article/1Panstrongylus geniculatus (Latreille, 1811) (Reduviidae: Triatominae) is a hematophagous bug generally associated with the wild cycle of Trypanosoma cruzi Chagas, 1909, the etiological agent of Chagas disease. The incursions of this insect into homes located in urban and peri-urban areas cause alarm in the population and are becoming more and more frequent. As a contribution to the available knowledge on the biology and ecology of P. geniculatus as a species that transmits T. cruzi in this type of environment, the objective was to explore the influence of six environmental variables (altitude, monthly precipitation, relative humidity, average temperature , solar radiation and wind speed) on the distribution of specimens of this species captured in homes of 12 localities of the Metropolitan Area of ​​Caracas (AMC). The parasitological evaluation of the 39 insects examined showed that about 90% of them presented flagellate forms in their feces. The largest number of specimens came from collections in localities of the Miranda state (n = 32), with reports being more common during the months of May and June. Principal Component Analysis (PCA) applied to these data as an exploratory tool concentrates 60% of the variance in the first two principal components and suggests monthly precipitation (mm) and relative humidity (%) as possible environmental variables. explanations of the presence of this species in homes of the AMC.Panstrongylus geniculatus (Latreille, 1811) (Reduviidae: Triatominae) es un chinche hematófago asociado generalmente al ciclo silvestre del Trypanosoma cruzi Chagas, 1909, agente etiológico de la Enfermedad de Chagas. Las incursiones de este insecto en domicilios ubicados en zonas urbanas y periurbanas causan alarma en la población y se hacen cada vez más frecuentes. Como un aporte al conocimiento disponible sobre la biología y ecología de P. geniculatus como especie transmisora de T. cruzi en este tipo de ambientes, se propuso como objetivo explorar la influencia de seis variables ambientales (altitud, precipitación mensual, humedad relativa, temperatura media, radiación solar y velocidad del viento) sobre la distribución de especímenes de esta especie capturados en domicilios de 12 localidades del Área Metropolitana de Caracas (AMC). La evaluación parasitológica de los 39 insectos examinados mostró que cerca del 90% de ellos presentaron formas flageladas en sus heces. La mayor cantidad de ejemplares provinieron de colectas en localidades del estado Miranda (n = 32), siendo más comunes los reportes durante los meses de mayo y junio. El Análisis de Componentes Principales (ACP) aplicado a estos datos la data como herramienta exploratoria concentra en los primeros dos componentes principales un 60% de la varianza y sugiere a la precipitación mensual (mm) y la humedad relativa (%) como posibles variables ambientales explicativas de la presencia de esta especie en domicilios del AMC

Analysis of the Dynamics of Infiltrating CD4+ T Cell Subsets in the Heart during Experimental Trypanosoma cruzi Infection

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects several million people in Latin America. Myocarditis, observed during both the acute and chronic phases of the disease, is characterized by an inammatory mononuclear cell infiltrate that includes CD4+ T cells. It is known that Th1 cytokines help to control infection. The role that Treg and Th17 cells may play in disease outcome, however, has not been completely elucidated. We performed a comparative study of the dynamics of CD4+ T cell subsets after infection with the T. cruzi Y strain during both the acute and chronic phases of the disease using susceptible BALB/c and non-susceptible C57BL/6 mice infected with high or low parasite inocula. During the acute phase, infected C57BL/6 mice showed high levels of CD4+ T cell infiltration and expression of Th1 cytokines in the heart associated with the presence of Treg cells. In contrast, infected BALB/c mice had a high heart parasite burden, low heart CD4+ T cell infiltration and low levels of Th1 and inflammatory cytokines, but with an increased presence of Th17 cells. Moreover, an increase in the expression of IL-6 in susceptible mice was associated with lethality upon infection with a high parasite load. Chronically infected BALB/c mice continued to present higher parasite burdens than C57BL/6 mice and also higher levels of IFN-γ, TNF, IL-10 and TGF-β. Thus, the regulation of the Th1 response by Treg cells in the acute phase may play a protective role in non-susceptible mice irrespective of parasite numbers. On the other hand, Th17 cells may protect susceptible mice at low levels of infection, but could, in association with IL-6, be pathogenic at high parasite loads. © 2013 Sanoja et al.Ministerio de Ciencia y Tecnología’’ (SAF2007-61716; SAF2005-02220); ‘‘Fondo de Investigaciones Sanitarias’’ (PS09/00538); ‘‘Red Temática de Investigación en Enfermedades cardiovasculares’’ (RECAVA RD06/0014/1013); ‘‘Red de Investigación de Centros de Enfermedades Tropicales’’ (RICET RD06/0021/0016); European Union (HEALTH-FE-2008-22303, ChagasEpiNet); ‘‘Universidad Autónoma de Madrid’’ and ‘‘Comunidad de Madrid’’ (CC08-UAM/SAL-4440/08); AECID cooperation with Argentine (A/025417/09) and ‘‘Fundación Ramón Areces’Peer Reviewe

Infected C57BL/6 mice showed greater numbers of cardiac infiltrating CD4⁺ T cells and more inflammation than infected BALB/c mice.

<p>BALB/c mice were infected with high inoculum (open bar) or low inoculum (open dashed bar). C57BL/6 mice were infected with high inoculum (filled bar) or low inoculum (filled dashed bar). (<b>A</b>) Immunofluorescence staining of heart tissue sections from BALB/c and C57BL/6 mice infected with high inoculum with anti-CD4 antibody at 14 d.p.i. (magnification: 630×). (<b>B</b>) Quantitative RT-PCR of total heart tissue RNA from non-infected (NI) mice and mice infected with either high inoculum (top) or low inoculum (bottom) at 7, 12, 17 and 22 d.p.i., utilizing the <i>Cd4</i> probe. (<b>C</b>) as for “B” utilizing the <i>Ifng, Il1a</i> and <i>Tnf</i> probes. Data were normalized with respect to NI mice (Fold change: 1) and represent at least two independent experiments performed with 3 mice per experimental group. Statistically significant differences between infected and non-infected mice (0 d.p.i.) and between BALB/c and C57BL/6 mice under each treatment are shown: *<i>p</i><0.05,**<i>p</i><0.01 and ***<i>p</i><0.001.</p