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Nat Immunol ; 20(2): 129-140, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30664762

RESUMO

Basophils are evolutionarily conserved in vertebrates, despite their small numbers and short life span, suggesting that they have beneficial roles in maintaining health. However, these roles are not fully defined. Here we demonstrate that basophil-deficient mice exhibit reduced bacterial clearance and increased morbidity and mortality in the cecal ligation and puncture (CLP) model of sepsis. Among the several proinflammatory mediators that we measured, tumor necrosis factor (TNF) was the only cytokine that was significantly reduced in basophil-deficient mice after CLP. In accordance with that observation, we found that mice with genetic ablation of Tnf in basophils exhibited reduced systemic concentrations of TNF during endotoxemia. Moreover, after CLP, mice whose basophils could not produce TNF, exhibited reduced neutrophil and macrophage TNF production and effector functions, reduced bacterial clearance, and increased mortality. Taken together, our results show that basophils can enhance the innate immune response to bacterial infection and help prevent sepsis.


Assuntos
Basófilos/imunologia , Endotoxemia/imunologia , Imunidade Inata , Fator de Necrose Tumoral alfa/imunologia , Transferência Adotiva , Animais , Basófilos/metabolismo , Ceco/microbiologia , Modelos Animais de Doenças , Endotoxemia/microbiologia , Endotoxemia/terapia , Microbioma Gastrointestinal , Humanos , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Taxa de Sobrevida , Fator de Necrose Tumoral alfa/genética
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