Splenic B1 B Cells Acquire a Proliferative and Anti-Inflamatory Profile During Pregnancy in Mice

B cells are a heterogeneous cell population with differential ontogeny, anatomical location, and functions. B1 B cells are a distinct subpopulation characterized by their unique capacity of self-renewal, the production of large quantities of IL-10, and the ability to secrete protective, anti-inflammatory natural antibodies (NAbs), presumably upon down-regulation of CD1d expression. Although natural antibodies are thought to be protective, due to their polyreactivity, their participation in certain autoimmune diseases has been suggested. In the context of pregnancy, the role of B1 B cells has been discussed controversially. While in human pregnancies B1 B cells and natural/polyreactive antibodies they produce are involved in the development of preeclampsia, in mice they promote healthy gestation and fetal protection. In this work, we aimed to functionally characterize the splenic B1 B cell population during pregnancy in mice. Functional enrichment analysis using only up-regulated transcripts from a transcriptomic profile performed on total splenic B cells from pregnant compared to non-pregnant mice showed augmented cell cycle and DNA replication pathways. Proliferation studies by flow cytometry showed augmented Ki-67 proliferation marker expression and percentages of B1 B cells. Furthermore, B1 B cells produced higher levels of IL-10 and lower levels of TNF-α leading to an increased IL-10/TNF-α ratio and showing an immunoregulatory phenotype. Finally, we observed lower expression of CD1d on B1 B cells, suggesting a higher capacity to produce NAbs in the context of pregnancy. In summary, our results showed not only an expanded and proliferative splenic B1 B cell population during pregnancy but also the acquisition of immunomodulatory capacities suggesting its critical role in the intricate process of pregnancy tolerance

The steroid-hormone ecdysone coordinates parallel pupariation neuromotor and morphogenetic subprograms via epidermis-to-neuron Dilp8-Lgr3 signal induction

Funding Information: We thank Drs. Carlos Ribeiro, Christen Mirth, Elio Sucena, Filip Port, Frank Schnorrer, Julien Colombani, Maria Dominguez, Maria Luisa Vasconcelos, Pierre Leopold, Simon Bullock, Rita Teodoro, Gerald Rubin, Melissa Harrison, Kate O’Connor-Giles, Jill Wildonger, Mariana Melani, Pablo Wappner, and Christian Wegener for fly stocks and reagents. We thank Ryohei Yagi and Konrad Basler for the LHV2 plasmid and Brain McCabe for the mhc-Gateway destination plasmid. We thank Carlos Ribeiro and Dennis Goldschmidt for help in designing and constructing one of the pupariation arenas and Mariana Melani, Pablo Wappner, Arash Bashirullah, and Filip Port for sharing resources and unpublished data. We thank Arash Bashirullah, Fillip Port, and Carlos Ribeiro for discussions and/or comments on the manuscript, and Jim Truman for discussions on Fraenkel’s pupariation factors. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. Work in the Integrative Biomedicine Laboratory was supported by the European Commission FP7 (PCIG13-GA-2013-618847), by the FCT (IF/00022/2012; Congento LISBOA-01-0145-FEDER-022170, cofinanced by FCT/Lisboa2020; UID/Multi/04462/2019; PTDC/BEXBCM/1370/2014; PTDC/MED-NEU/30753/2017; PTDC/BIA-BID/31071/2017; FCT SFRH/BPD/94112/ 2013; SFRH/BD/94931/2013), the MIT Portugal Program (MIT-EXPL/BIO/0097/2017), and FAPESP (16/09659-3, 16/10342-4, and 17/17904-0). AG is a CONICET researcher, YV holds a CONICET postdoctoral fellowship and FPS and MJD hold a PhD fellowship from CONICET. Work in the Garelli lab was supported by ANPCyT (Agencia Nacional para la Promoción de la Ciencia y la Tecnología, PICT 2014-2900 and PICT 2017-0254) and CONICET (PIP11220150100182CO). Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.Innate behaviors consist of a succession of genetically-hardwired motor and physiological subprograms that can be coupled to drastic morphogenetic changes. How these integrative responses are orchestrated is not completely understood. Here, we provide insight into these mechanisms by studying pupariation, a multi-step innate behavior of Drosophila larvae that is critical for survival during metamorphosis. We find that the steroid-hormone ecdysone triggers parallel pupariation neuromotor and morphogenetic subprograms, which include the induction of the relaxin-peptide hormone, Dilp8, in the epidermis. Dilp8 acts on six Lgr3-positive thoracic interneurons to couple both subprograms in time and to instruct neuromotor subprogram switching during behavior. Our work reveals that interorgan feedback gates progression between subunits of an innate behavior and points to an ancestral neuromodulatory function of relaxin signaling.publishersversionpublishe

Controle do vetor do dengue e participação da comunidade em Catanduva, São Paulo, Brasil Dengue vector control and community participation in Catanduva, São Paulo State, Brazil

O trabalho teve o objetivo de identificar mudanças de conhecimentos e práticas de prevenção do dengue, e desenvolveu-se em duas áreas de Catanduva: Área de Estudo e Área Controle. Realizaram-se, entre 1999 e 2001, levantamentos quantitativo inicial e qualitativo; diagnóstico preliminar, apresentado à comunidade da Área de Estudo, desencadeando discussão para a definição e o direcionamento das ações; o desenvolvimento das ações na Área de Estudo, com a participação da comunidade; continuidade das atividades de rotina na Área Controle; e avaliação final. Na Área de Estudo, as ações realizadas foram: mudança do trabalho dos agentes de controle de vetores que passaram a demonstrar as medidas preventivas, sem a retirada de recipientes e sem utilização de larvicida; utilização de material educativo específico à realidade local; atividades relacionadas às prioridades dos moradores; atividades como música, teatro, gincanas e brincadeiras; demonstração do ciclo do vetor. Como resultado, houve a diminuição significante do número de recipientes por casa; o aumento significante da proporção de casas sem recipientes; e o aumento significante da proporção de pessoas que reconheceram as larvas do vetor na Área de Estudo em relação à de Controle.<br>This study aimed to identify changes in knowledge and practices learned to prevent dengue fever in two areas of Catanduva, São Paulo State, from 1999 to 2001: a study area and a control area. The study included an initial quantitative survey, qualitative research, a preliminary diagnosis presented to the community to launch a discussion aimed at defining future actions, implementation of the actions in the study area with community participation (but without changes in the control area), and a final comparison of the two areas. Changes in the study area included: vector control workers began demonstrating preventive measures without removing potential breeding places or using larvicide; use of educational aids specific to the local reality; activities related to the residents’ priorities; and activities such as music, theater skits, scavenger hunts, and games to demonstrate the vector cycle. Potential domiciliary breeding sites were significantly reduced; the proportion of houses without breeding sites was significantly increased; and there was an increase in the percentage of individuals who recognized the larval form of the vector in the study area as compared to the control area