Role of the cGAS/STING pathway in the control of Brucella abortus infection acquired through the respiratory route

Despite the importance of the respiratory route for Brucella transmission, the lung immune response to this pathogen is scarcely characterized. We investigated the role of the cGAS/STING pathway of microbial DNA recognition in the control of respiratory Brucella infection. After in vitro B. abortus infection, CFU numbers were significantly higher in alveolar macrophages (AM) and lung explants from STING KO mice than in samples from wild type (WT) mice, but no difference was observed for cGAS KO samples. CFU were also increased in WT AM and lung epithelial cells preincubated with the STING inhibitor H151. Several proinflammatory cytokines (TNF-α, IL-1β, IL-6, IP-10/CXCL10) were diminished in Brucella-infected lung explants and/or AM from STING KO mice and cGAS KO mice. These cytokines were also reduced in infected AM and lung epithelial cells pretreated with H151. After intratracheal infection with B. abortus, STING KO mice exhibited increased CFU in lungs, spleen and liver, a reduced expression of IFN-β mRNA in lungs and spleen, and reduced levels of proinflammatory cytokines and chemokines in bronchoalveolar lavage fluid (BALF) and lung homogenates. Increased lung CFU and reduced BALF cytokines were also observed in cGAS KO mice. In summary, the cGAS/STING pathway induces the production of proinflammatory cytokines after respiratory Brucella infection, which may contribute to the STING-dependent control of airborne brucellosis

Ayahuasca and Its DMT- and β-carbolines – Containing Ingredients Block the Expression of Ethanol-Induced Conditioned Place Preference in Mice: Role of the Treatment Environment

Ayahuasca is a hallucinogenic beverage produced from the decoction of Banisteriopsis caapi (Bc) and Psychotria viridis (Pv), β-carboline- and N,N-dimethyltryptamine(DMT)-containing plants, respectively. Accumulating evidence suggests that ayahuasca may have therapeutic effects on ethanol abuse. It is not known, however, whether its effects are dependent on the presence of DMT or if non-DMT-containing components would have therapeutic effects. The aim of the present study was to investigate the rewarding properties of ayahuasca (30, 100, and 300 mg/kg, orally), Bc (132, 440, and 1320 mg/kg, orally) and Pv (3.75, 12.5 and 37.5 mg/kg, i.p.) extracts and their effects on ethanol (1.8 g/kg, i.p.) reward using the conditioned place preference (CPP) paradigm in male mice. Animals were conditioned with ayahuasca, Bc or Pv extracts during 8 sessions. An intermediate, but not a high, dose of ayahuasca induced CPP in mice. Bc and Pv did not induce CPP. Subsequently, the effects of those extracts were tested on the development of ethanol-induced CPP. Ayahuasca, Bc or Pv were administered before ethanol injections during conditioning sessions. While Bc and Pv exerted no effects on ethanol-induced CPP, pretreatment with ayahuasca blocked the development of CPP to ethanol. Finally, the effects of a post-ethanol-conditioning treatment with ayahuasca, Bc or Pv on the expression of ethanol-induced CPP were tested. Animals were conditioned with ethanol, and subsequently treated with either ayahuasca, Bc or Pv in the CPP environment previously associated with saline or ethanol for 6 days. Animals were then reexposed to ethanol and ethanol-induced CPP was quantified on the following day. Treatment with all compounds in the ethanol-paired environment blocked the expression of ethanol-induced CPP. Administration of an intermediate, but not a high, dose of ayahuasca and Bc, as well as Pv administration, in the saline-paired compartment blocked the expression of ethanol-induced CPP. The present study sheds light into the components underlying the therapeutic effects of ayahuasca on ethanol abuse, indicating that ayahuasca and its plant components can decrease ethanol reward at doses that do not exert abuse liability. Importantly, the treatment environment seems to influence the therapeutic effects of ayahuasca and Bc, providing important insights into clinical practice

Booster dose after 10 years is recommended following 17DD-YF primary vaccination

Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Governo do Estado de Minas Gerais. Secretaria de Estado de Saúde. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Universidade Federal de Alfenas. Alfenas, MG, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Assessoria Clínica de Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Assessoria Clínica de Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Ministerio da Saude. Secretaria de Vigilancia em Saude. Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Brasil.Universidade de Brasília. Brasilia, DF, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.US Food and Drug Administration. Center for Biologics Evaluation and Research. Silver Spring, MD USAFundação Oswaldo Cruz. Diretoria Regional de Brasília. Brasília, DF, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Publica. Rio de Janeiro, DF, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.A single vaccination of Yellow Fever vaccines is believed to confer life-long protection. In this study, results of vaccinees who received a single dose of 17DD-YF immunization followed over 10 y challenge this premise. YF-neutralizing antibodies, subsets of memory T and B cells as well as cytokine-producing lymphocytes were evaluated in groups of adults before (NVday0) and after (PVday30-45, PVyear1-4, PVyear5-9, PVyear10-11, PVyear12-13) 17DD-YF primary vaccination. YF-neutralizing antibodies decrease significantly from PVyear1-4 to PVyear12-13 as compared to PVday30-45, and the seropositivity rates (PRNT≥2.9Log10mIU/mL) become critical (lower than 90%) beyond PVyear5-9. YF-specific memory phenotypes (effector T-cells and classical B-cells) significantly increase at PVday30-45 as compared to na've baseline. Moreover, these phenotypes tend to decrease at PVyear10-11 as compared to PVday30-45. Decreasing levels of TNF-α(+) and IFN-γ(+) produced by CD4(+) and CD8(+) T-cells along with increasing levels of IL-10(+)CD4(+)T-cells were characteristic of anti-YF response over time. Systems biology profiling represented by hierarchic networks revealed that while the na've baseline is characterized by independent micro-nets, primary vaccinees displayed an imbricate network with essential role of central and effector CD8(+) memory T-cell responses. Any putative limitations of this cross-sectional study will certainly be answered by the ongoing longitudinal population-based investigation. Overall, our data support the current Brazilian national immunization policy guidelines that recommend one booster dose 10 y after primary 17DD-YF vaccination