O receptor de eferocitose Axl controla o recrutamento de macrófagos alveolares para as mucosas pulmonares durante a homeostase e regula a inflamação pulmonar

A mucosa pulmonar é um microambiente constantemente exposto à entrada de patógenos e devido a sua função fisiológica de trocas gasosas, é bastante sensível aos danos colaterais das respostas imunológicas. Desse modo, as respostas inflamatórias e tolerogênicas precisam ser finamente controladas nestes locais. Macrófagos alveolares (AMs) são constantemente estimulados por antígenos e sua ativação deve ser finamente regulada para evitar danos ao tecido pulmonar. Além de seu papel na fagocitose de microrganismos, AMs são as principais células que fagocitam células apoptóticas (eferocitose), contribuindo para a imunidade e homeostase nos pulmões. O receptor Axl, da família TAM, é expresso por células do sistema imunológico e além de mediar a eferocitose, bloqueia as vias de sinalização pró-inflamatórias dos TLRs e de citocinas. Nesse estudo, investigamos o papel do receptor Axl no recrutamento de AMs para as mucosas pulmonares, e na regulação de vias pró-inflamatórias durante a homeostase e silicose. Primeiramente a expressão do receptor Axl foi confirmada em células pulmonares totais e, especificamente em AMs. Analisando comparativamente os percentuais de AMs, caracterizados pela marcação duplo positiva para Siglec F+ e CD11c+, durante a homeostase, observamos que o BAL de camundongos selvagens possui em média 37% de AMs, enquanto que o BAL de camundongos Axl-/- possui em média, 65% de AMs. Além do aumento do recrutamento de AMs, observamos uma menor concentração de TGF-β e IL-10 nos BALs de camundongos Axl-/- se comparados aos selvagens, durante a homeostase. AMs de camundongos Axl-/- e selvagens quando estimulados in vitro com LPS, não apresentam diferenças entre si, no que diz respeito à produção de citocinas, porém o LPS em combinação com neutrófilos apoptóticos opsonizados com Gas6 provoca uma diminuição de TNF-α e aumento de IL-6 nos camundongos Axl-/- em relação aos selvagens. Durante a silicose, observamos um aumento no número total de células nos BALs de ambos os animais, porém existe uma diminuição de AMs em camundongos Axl-/- e selvagens. Investigando o perfil celular que se encontrava aumentado durante a silicose, observamos que o percentual de neutrófilos (CD11b+Ly6G+) nos BALs de camundongos Axl-/- estava aumentado, se comparados aos selvagens. Também observamos diminuição nas concentrações de IL-10 nos BALs de camundongos silicóticos selvagens e deficientes em Axl, em relação aos BALs dos mesmos grupos instilados com PBS e nenhuma diferença nas concentrações de TGF-β nesses grupos. A instilação de sílica provocou amento da concentração de TNF-α nos BALs de camundongos deficientes em Axl, mas não em camundongos selvagens e um aumento de IL-6 nos BALs de camundongos selvagens, mas não nos BALs de camundongos deficientes em Axl. Coletivamente, nossos dados indicam que o bloqueio da eferocitose mediada por Axl e deficiências na regulação negativa da sinalização pró-inflamatória intracelular pelo receptor Axl resulta no aumento do recrutamento de AMs durante a homeostase e, além disso essas células apresentam um potencial regulatório, devido ao perfil de citocinas secretadas durante a homeostase. Durante a silicose, existe um possível aumento de morte de AMs, sugerindo que há um controle menor do processo inflamatório em camundongos Axl-/-. O aumento maior no recrutamento de neutrófilos nos camundongos Axl-/- corrobora a hipótese de menor controle do processo inflamatório

Trypanosoma cruzi Infection Induces Cellular Stress Response and Senescence-Like Phenotype in Murine Fibroblasts

Trypanosoma cruzi infects and replicates within a wide variety of immune and non-immune cells. Here, we investigated early cellular responses induced in NIH-3T3 fibroblasts upon infection with trypomastigote forms of T. cruzi. We show that fibroblasts were susceptible to T. cruzi infection and started to release trypomastigotes to the culture medium after 4 days of infection. Also, we found that T. cruzi infection reduced the number of fibroblasts in 3-day cell cultures, by altering fibroblast proliferation. Infected fibroblasts displayed distinctive phenotypic alterations, including enlarged and flattened morphology with a nuclei accumulation of senescence-associated heterochromatin foci. In addition, infection induced an overexpression of the enzyme senescence-associated β-galactosidase (SA-β-gal), an activation marker of the cellular senescence program, as well as the production of cytokines and chemokines involved with the senescence-associated secretory phenotype (SASP) such as IL-6, TNF-α, IL-1β, and MCP-1. Infected fibroblasts released increased amounts of stress-associated factors nitric oxide (NO) and reactive oxygen species (ROS), and the treatment with antioxidants deferoxamine (DFO) and N-acetylcysteine reduced ROS generation, secretion of SASP-related cytokine IL-6, SA-β-gal activity, and parasite load by infected fibroblasts. Taken together, our data suggest that T. cruzi infection triggers a rapid cellular stress response followed by induction of a senescent-like phenotype in NIH-3T3 fibroblasts, enabling them to act as reservoirs of parasites during the early stages of the Chagas disease

Regulator of G-protein signaling 1 critically supports CD8+ TRM cell-mediated intestinal immunity.

Members of the Regulator of G-protein signaling (Rgs) family regulate the extent and timing of G protein signaling by increasing the GTPase activity of Gα protein subunits. The Rgs family member Rgs1 is one of the most up-regulated genes in tissue-resident memory (TRM) T cells when compared to their circulating T cell counterparts. Functionally, Rgs1 preferentially deactivates Gαq, and Gαi protein subunits and can therefore also attenuate chemokine receptor-mediated immune cell trafficking. The impact of Rgs1 expression on tissue-resident T cell generation, their maintenance, and the immunosurveillance of barrier tissues, however, is only incompletely understood. Here we report that Rgs1 expression is readily induced in naïve OT-I T cells in vivo following intestinal infection with Listeria monocytogenes-OVA. In bone marrow chimeras, Rgs1 -/- and Rgs1 +/+ T cells were generally present in comparable frequencies in distinct T cell subsets of the intestinal mucosa, mesenteric lymph nodes, and spleen. After intestinal infection with Listeria monocytogenes-OVA, however, OT-I Rgs1 +/+ T cells outnumbered the co-transferred OT-I Rgs1- /- T cells in the small intestinal mucosa already early after infection. The underrepresentation of the OT-I Rgs1 -/- T cells persisted to become even more pronounced during the memory phase (d30 post-infection). Remarkably, upon intestinal reinfection, mice with intestinal OT-I Rgs1 +/+ TRM cells were able to prevent the systemic dissemination of the pathogen more efficiently than those with OT-I Rgs1 -/- TRM cells. While the underlying mechanisms are not fully elucidated yet, these data thus identify Rgs1 as a critical regulator for the generation and maintenance of tissue-resident CD8+ T cells as a prerequisite for efficient local immunosurveillance in barrier tissues in case of reinfections with potential pathogens

A IMPORTÂNCIA DO ENFERMEIRO NOS SERVIÇOS DE HEMODINÂMICA: UMA REVISÃO INTEGRATIVA

No início do século XX as doenças cardiovasculares provocavam 10% dos óbitos no mundo. Com o objetivo de melhorar a estratégia de tratamento dessas doenças surgem procedimentos com resultados favoráveis, os quais estão inclusos na cardiologia intervencionista, a qual é desenvolvida em Unidades de Hemodinâmica, sendo eles: a angioplastia primária e o emprego de stents. A experiência do médico e de toda a equipe de enfermagem e radiologia é um fator essencial para o resultado obtido nos procedimentos empregados na cardiologia intervencionista. O presente artigo consiste em uma revisão integrativa, no qual tem como objetivo discorrer acerca da importância do enfermeiro nos serviços de hemodinâmica, com o intuito de conscientizar os estudantes e profissionais da área acerca da sua importância nesse setor. Trata-se de uma revisão de literatura do tipo integrativa, na qual foi realizada uma pesquisa bibliográfica, nas bases de dados da Biblioteca Virtual da Saúde: Sistema Latino Americano e do Caribe de informação em Ciências da Saúde e na Biblioteca Eletrônica Científica Online, acerca do tema em estudo. A atuação da Enfermagem no serviço de hemodinâmica cardíaca é de suma importância, visto que tem como objetivo um melhor planejamento do cuidado por meio da Sistematização da Assistência de Enfermagem. Em suma, é possível concluir que as Unidades de Hemodinâmica exigem do enfermeiro conhecimentos referentes à administração e à assistência ao indivíduo, estendendo-se à família e à comunidade

Perceptions of women who used psycho-active substances during the management of the professional attendance

This study aimed to know the perceptions of women who used psychoactive substances during pregnancy regarding the care of the professional. The descriptive-exploratory method followed with a qualitative approach. Eleven women who used alcohol and / or other psychoactive substances during pregnancy participated in the study. Data collection was carried out between March and May 2017 through a semi-structured recorded interview. Content analysis was used, in light of the Peplau Theory. From the narratives, two categories emerged: discovery of the addict’s condition by the professional and positive and negative points in the consultations. The study participants demonstrated satisfaction with the prenatal consultations, but indicated as negative the delay in attendance, the difficult communication of doctors and disrespectful forms in the hospital care, through situations of violence. Therefore, it is important to review the assistance offered to pregnant women, especially as drug users, in order to mitigate unfavorable maternal-fetal prognoses and not to prejudice the construction and maintenance of interpersonal relationships between clients and professionals

Association Between The Sexual Activity And Acquired Immunity Markers In Women With Aids In A Brazilian Northeast County

INTRODUCTION: Acquired Immunodeficiency Syndrome (AIDS) comes along the years promoting inversion of the relation men/women, committing mainly the productive and reproductive life phase women. The sexuality, inherent upon human being, has in the expression of satisfaction of the sexual performance the possibility of providing several benefits in the quality of life of people, and CD4+ T- lymphocytes are the main marker of immunity of the women living with Aids. OBJECTIVE: This study aims to show up the association between the CD4 count and the sexual performance of women living with AIDS in Imperatriz city. METHODOLOGY: cross-sectional analytical study, carried out in 10 months, selecting women  using antiretroviral therapy at least six months, including those older than 18, having sexual practice before having AIDS, able to answer two questionnaires. Socio-demographic facts were recorded in own form, and sexual performance in the FSFI questionnaire. The sample based in 479 women, sampling error 5%, confidence interval 95%, alpha value ≤ 5%, included 149 women. Chi-square test was used to evaluate the association between the variables. RESULT: The larger FSFI score means and medians coincided with the highest means of CD4 T- lymphocyte count (Kruskal Wallis test, p = 0.0347), and a positive association between FSFI and the CD4 / CD8 ratio (Spearman test, p = 0.0264), confirming the alternative hypothesis. CONCLUSION: In this sample there was a positive association between sexual performance /sexual activity, with or without a condom, with CD4 T- lymphocyte count and CD4 / CD8 ratio. &nbsp

Video_2_Regulator of G-protein signaling 1 critically supports CD8+ TRM cell-mediated intestinal immunity.mp4

Members of the Regulator of G-protein signaling (Rgs) family regulate the extent and timing of G protein signaling by increasing the GTPase activity of Gα protein subunits. The Rgs family member Rgs1 is one of the most up-regulated genes in tissue-resident memory (TRM) T cells when compared to their circulating T cell counterparts. Functionally, Rgs1 preferentially deactivates Gαq, and Gαi protein subunits and can therefore also attenuate chemokine receptor-mediated immune cell trafficking. The impact of Rgs1 expression on tissue-resident T cell generation, their maintenance, and the immunosurveillance of barrier tissues, however, is only incompletely understood. Here we report that Rgs1 expression is readily induced in naïve OT-I T cells in vivo following intestinal infection with Listeria monocytogenes-OVA. In bone marrow chimeras, Rgs1-/- and Rgs1+/+ T cells were generally present in comparable frequencies in distinct T cell subsets of the intestinal mucosa, mesenteric lymph nodes, and spleen. After intestinal infection with Listeria monocytogenes-OVA, however, OT-I Rgs1+/+ T cells outnumbered the co-transferred OT-I Rgs1-/- T cells in the small intestinal mucosa already early after infection. The underrepresentation of the OT-I Rgs1-/- T cells persisted to become even more pronounced during the memory phase (d30 post-infection). Remarkably, upon intestinal reinfection, mice with intestinal OT-I Rgs1+/+ TRM cells were able to prevent the systemic dissemination of the pathogen more efficiently than those with OT-I Rgs1-/- TRM cells. While the underlying mechanisms are not fully elucidated yet, these data thus identify Rgs1 as a critical regulator for the generation and maintenance of tissue-resident CD8+ T cells as a prerequisite for efficient local immunosurveillance in barrier tissues in case of reinfections with potential pathogens.</p

DataSheet_2_Regulator of G-protein signaling 1 critically supports CD8+ TRM cell-mediated intestinal immunity.docx

Members of the Regulator of G-protein signaling (Rgs) family regulate the extent and timing of G protein signaling by increasing the GTPase activity of Gα protein subunits. The Rgs family member Rgs1 is one of the most up-regulated genes in tissue-resident memory (TRM) T cells when compared to their circulating T cell counterparts. Functionally, Rgs1 preferentially deactivates Gαq, and Gαi protein subunits and can therefore also attenuate chemokine receptor-mediated immune cell trafficking. The impact of Rgs1 expression on tissue-resident T cell generation, their maintenance, and the immunosurveillance of barrier tissues, however, is only incompletely understood. Here we report that Rgs1 expression is readily induced in naïve OT-I T cells in vivo following intestinal infection with Listeria monocytogenes-OVA. In bone marrow chimeras, Rgs1-/- and Rgs1+/+ T cells were generally present in comparable frequencies in distinct T cell subsets of the intestinal mucosa, mesenteric lymph nodes, and spleen. After intestinal infection with Listeria monocytogenes-OVA, however, OT-I Rgs1+/+ T cells outnumbered the co-transferred OT-I Rgs1-/- T cells in the small intestinal mucosa already early after infection. The underrepresentation of the OT-I Rgs1-/- T cells persisted to become even more pronounced during the memory phase (d30 post-infection). Remarkably, upon intestinal reinfection, mice with intestinal OT-I Rgs1+/+ TRM cells were able to prevent the systemic dissemination of the pathogen more efficiently than those with OT-I Rgs1-/- TRM cells. While the underlying mechanisms are not fully elucidated yet, these data thus identify Rgs1 as a critical regulator for the generation and maintenance of tissue-resident CD8+ T cells as a prerequisite for efficient local immunosurveillance in barrier tissues in case of reinfections with potential pathogens.</p

DataSheet_4_Regulator of G-protein signaling 1 critically supports CD8+ TRM cell-mediated intestinal immunity.zip

Members of the Regulator of G-protein signaling (Rgs) family regulate the extent and timing of G protein signaling by increasing the GTPase activity of Gα protein subunits. The Rgs family member Rgs1 is one of the most up-regulated genes in tissue-resident memory (TRM) T cells when compared to their circulating T cell counterparts. Functionally, Rgs1 preferentially deactivates Gαq, and Gαi protein subunits and can therefore also attenuate chemokine receptor-mediated immune cell trafficking. The impact of Rgs1 expression on tissue-resident T cell generation, their maintenance, and the immunosurveillance of barrier tissues, however, is only incompletely understood. Here we report that Rgs1 expression is readily induced in naïve OT-I T cells in vivo following intestinal infection with Listeria monocytogenes-OVA. In bone marrow chimeras, Rgs1-/- and Rgs1+/+ T cells were generally present in comparable frequencies in distinct T cell subsets of the intestinal mucosa, mesenteric lymph nodes, and spleen. After intestinal infection with Listeria monocytogenes-OVA, however, OT-I Rgs1+/+ T cells outnumbered the co-transferred OT-I Rgs1-/- T cells in the small intestinal mucosa already early after infection. The underrepresentation of the OT-I Rgs1-/- T cells persisted to become even more pronounced during the memory phase (d30 post-infection). Remarkably, upon intestinal reinfection, mice with intestinal OT-I Rgs1+/+ TRM cells were able to prevent the systemic dissemination of the pathogen more efficiently than those with OT-I Rgs1-/- TRM cells. While the underlying mechanisms are not fully elucidated yet, these data thus identify Rgs1 as a critical regulator for the generation and maintenance of tissue-resident CD8+ T cells as a prerequisite for efficient local immunosurveillance in barrier tissues in case of reinfections with potential pathogens.</p