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Nat Immunol. 2019 Feb;20(2):129-140. doi: 10.1038/s41590-018-0288-7. Epub 2019 Jan 21.

Basophil-derived tumor necrosis factor can enhance survival in a sepsis model in mice.

Author information

1
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA. adrian.piliponsky@seattlechildrens.org.
2
Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA. adrian.piliponsky@seattlechildrens.org.
3
Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA. adrian.piliponsky@seattlechildrens.org.
4
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA.
5
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
6
Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
7
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
8
Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, USA.
9
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.

Abstract

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.

PMID:
30664762
PMCID:
PMC6352314
[Available on 2019-07-21]
DOI:
10.1038/s41590-018-0288-7

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