PXD035577-1

PXD035577 is an original dataset announced via ProteomeXchange.

Title	Age-related decline in the resistance of mice to bacterial infection and in LPS/TLR4 pathway-dependent neutrophil responses
Description	Host defense against bacterial and fungal infections diminishes with age. In humans, this is thought to be caused in part by a decline in neutrophil responses. However, it remains unclear whether a similar decline in neutrophil function occurs in mice. Here, we show that old mice have a reduced capacity to clear pathogenic E. coli during septic peritonitis. Neutrophil recruitment to the peritoneum was elevated during lipopolysaccharide (LPS)-induced septic peritonitis but not aseptic peritonitis. Neutrophils from old mice showed reduced chemoattractant-induced reactive oxygen species (ROS) production upon priming with LPS but not GM-CSF/TNF. Phagocytosis and degranulation were reduced in a partially LPS-dependent manner, whereas NETosis was impaired independently of LPS. The chemoattractant-stimulated production of PIP3 was reduced upon priming with LPS but not GM-CSF/TNF, whereas PI(4,5)P2 levels were constitutively low. Unexpectedly, chemotaxis was normal regardless of priming pathway, as were the chemoattractant-stimulated activities of Rac1 and Rac2. The expression of 5% of neutrophil proteins was deregulated in old age. Granule proteins, particularly cathepsins and serpins, as well as toll-like receptor (TLR) pathway proteins and membrane receptors were upregulated, whereas chromatin and RNA regulators were downregulated. Upregulation of Cd180 and downregulation of MyD88 may contribute to the impaired LPS priming and LPS-dependent PIP3 production. In summary, all major neutrophil responses except chemotaxis decline with age in mice, particularly upon LPS priming. This LPS-TLR4 pathway dependence resolves some of the controversy regarding the effects of age on murine neutrophils and confirms mice are an appropriate model for the declining human neutrophil function.
HostingRepository	PRIDE
AnnounceDate	2022-08-20
AnnouncementXML	Submission_2022-08-20_13:03:22.289.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Oxley
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-25 02:32:09	ID requested
⏵ 1	2022-08-20 13:03:22	announced

Dataset with its publication pending

submitter keyword: aging, neutrophils, TLR4, ROS, degranulation, phagocytosis, NETs

david oxley
contact affiliation	Babraham Institute
contact email	david.oxley@babraham.ac.uk
lab head
David Oxley
contact affiliation	Babraham Institute
contact email	david.oxley@babraham.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035577
     1. Label: PRIDE project
     2. Name: Age-related decline in the resistance of mice to bacterial infection and in LPS/TLR4 pathway-dependent neutrophil responses