ABSTRACT
Increasing attention has been directed to cytotoxic CD4+ T cells (CD4CTLs) in different pathologies, both in humans and mice. The impact of CD4CTLs in immunity and the mechanisms controlling their generation, however, remain poorly understood. Here, we show that CD4CTLs abundantly differentiate during mouse infection with the intracellular parasite Trypanosoma cruzi. CD4CTLs display parallel kinetics to Th1 cells in the spleen, mediate specific cytotoxicity against cells presenting pathogen-derived antigens and express immunoregulatory and/or exhaustion markers. We demonstrate that CD4CTL absolute numbers and activity are severely reduced in both Myd88-/- and Il18ra-/- mice. Of note, the infection of mixed-bone marrow chimeras revealed that wild-type (WT) but not Myd88-/- cells transcribe the CD4CTL gene signature and that Il18ra-/- and Myd88-/- CD4+ T cells phenocopy each other. Moreover, adoptive transfer of WT CD4+GzB+ T cells to infected Il18ra-/- mice extended their survival. Importantly, cells expressing the CD4CTL phenotype predominate among CD4+ T cells infiltrating the infected mouse cardiac tissue and are increased in the blood of Chagas patients, in which the frequency of CD4CTLs correlates with the severity of cardiomyopathy. Our findings describe CD4CTLs as a major player in immunity to a relevant human pathogen and disclose T-cell intrinsic IL-18R/MyD88 signaling as a key pathway controlling the magnitude of the CD4CTL response.
Subject(s)
Chagas Disease , Trypanosoma cruzi , Animals , CD4-Positive T-Lymphocytes , Humans , Mice , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Signal Transduction , Th1 CellsABSTRACT
Avaliar o gerenciamento dos resíduos de serviços de saúde gerados em três hospitais públicos localizados no estado de Mato Grosso do Sul (Brasil), incluindo parâmetros quali e quantitativos. Métodos: Tratou-se de um estudo descritivo observacional. Avaliou-se o gerenciamento dos resíduos gerados em dois hospitais públicos de grande porte (HG1, 240 leitos e HG2, 343 leitos) e um de pequeno porte (HP, 35 leitos). Os dados foram obtidos in situ, por observação direta dos procedimentos relativos ao gerenciamento dos resíduos e quantificação das massas dos resíduos gerados por setor, nos três hospitais. Resultados: O estudo revelou que o gerenciamento interno dos resíduos gerados nos três estabelecimentos de saúde não era adequado, e que os seus trabalhadores não haviam sido capacitados quanto ao correto manejo dos resíduos e ao uso de equipamentos de proteção individual. As taxas médias de geração de resíduos determinadas no HG1, HG2 e HP foram, respectivamente, de 4,7, 4,8 e 2,4 Kg.leito-1.dia-1, que se ajustam a faixas de valores descritos na literatura. Conclusão: As inadequações detectadas colocam diretamente em risco a saúde dos trabalhadores e de outros frequentadores dos três hospitais avaliados, bem como pessoas da comunidade externa, que podem ser expostos a patógenos ou agentes tóxicos presentes em tais resíduos.
To assess the management of health service waste generated in three public hospitals of Mato Grosso do Sul (Brazil), including qualitative and quantitative parameters. Methods: This was an observational and descriptive study. We assessed the waste management in two large public hospitals (HG1, 240 hospital beds and HG2, 343 beds) and in a small sized one (HP, 35 hospital beds). The data were collected in situ, by direct observation of the procedures for waste management and by quantifying the mass of waste generated by working sector in the three hospitals. Results: The study revealed that the internal management of waste generated in the three health care unities was not adequate, and that their workers were not trained on the proper management of waste and the use of personal protective equipment. The average rates of waste generation determined in HG1, HG2 and HP were, respectively, 4.7, 4.8 and 2.4 Kg.hospital bed-1.day-1, that fit the range of values reported in the literature. Conclusion: The detected inadequacies directly put at risk the health of workers and others who attend the three assessed hospitals and the outside comunity, which may be exposed to pathogens or toxic agents present in such waste.
