ArticlePLoS pathogens2023
Gas6 ameliorates intestinal mucosal immunosenescence to prevent the translocation of a gut pathobiont, Klebsiella pneumoniae, to the liver.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Ecology of protection: probiotic biogeography and sepsis prevention in the neonatal intestine.mBio · 2026Article
- Qingxuan Zhike Granules Modulate Gut Dysbiosis and Enhance Intestinal Repair in MurineJournal of microbiology and biotechnology · 2026Article
- Molecular and mechanistic insights into the gut-liver axis inInfection and immunity · 2026Review
- Gut Commensal Klebsiella pneumoniae Extracellular Vesicles Shape a Liver Microenvironment Conducive to Gut-Liver Bacterial Translocation and Pro-Tumorigenic Processes.Journal of extracellular vesicles · 2026Article
- Overcoming phagocytosis resistance of hypervirulentMicrobial cell (Graz, Austria) · 2026Article
- Pulmonary Abscess, Endophthalmitis, and Lumbar Spine Infection Attributable to InvasiveInfection and drug resistance · 2026Article
- SLAMF7 regulates goblet cell mucus production and negatively impacts gut homeostasis and commensalism.Gut microbes · 2025Article
- Probiotic biogeography and sepsis prevention in the neonatal intestine.bioRxiv : the preprint server for biology · 2025Article
- Bacillus coagulans alleviates hepatic injury caused by Klebsiella pneumoniae in rabbits.PloS one · 2025Article
- Immune aging and infectious diseases.Chinese medical journal · 2024Review
- Liver abscess induced by intestinal hypervirulentiScience · 2024Article
- GAS6 as a potential target to alleviate neuroinflammation during Japanese encephalitis in mouse models.Journal of neuroinflammation · 2024Article
- GAS6/TAM Axis as Therapeutic Target in Liver Diseases.Seminars in liver disease · 2024Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunosenescence refers to the development of weakened and/or dysfunctional immune responses associated with aging. Several commensal bacteria can be pathogenic in immunosuppressed individuals. Although Klebsiella pneumoniae is a commensal bacterium that colonizes human mucosal surfaces, the gastrointestinal tract, and the oropharynx, it can cause serious infectious diseases, such as pneumonia, urinary tract infections, and liver abscesses, primarily in elderly patients. However, the reason why K. pneumoniae is a more prevalent cause of infection in the elderly population remains unclear. This study aimed to determine how the host's intestinal immune response to K. pneumoniae varies with age. To this end, the study analyzed an in vivo K. pneumoniae infection model using aged mice, as well as an in vitro K. pneumoniae infection model using a Transwell insert co-culture system comprising epithelial cells and macrophages. In this study, we demonstrate that growth arrest-specific 6 (Gas6), released by intestinal macrophages that recognize K. pneumoniae, inhibits bacterial translocation from the gastrointestinal tract by enhancing tight-junction barriers in the intestinal epithelium. However, in aging mice, Gas6 was hardly secreted under K. pneumoniae infection due to decreasing intestinal mucosal macrophages; therefore, K. pneumoniae can easily invade the intestinal epithelium and subsequently translocate to the liver. Moreover, the administration of Gas6 recombinant protein to elderly mice prevented the translocation of K. pneumoniae from the gastrointestinal tract and significantly prolonged their survival. From these findings, we conclude that the age-related decrease in Gas6 secretion in the intestinal mucosa is the reason why K. pneumoniae can be pathogenic in the elderly, thereby indicating that Gas6 could be effective in protecting the elderly against infectious diseases caused by gut pathogens.
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