Cited by 189Immune Response and InflammationGut microbiota and healthImmune responses and vaccinations

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Early Innate Immunity to Bacterial Infection in the Lung Is Regulated Systemically by the Commensal Microbiota via Nod-Like Receptor Ligands

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Clarke, Thomas B.·2014·Infection and Immunity

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Abstract

The commensal microbiota is a major regulator of the immune system. The majority of commensal bacteria inhabit the gastrointestinal tract and are known to regulate local mucosal defenses against intestinal pathogens. There is growing appreciation that the commensal microbiota also regulates immune responses at extraintestinal sites. Currently, however, it is unclear how this influences host defenses against bacterial infection outside the intestine. Microbiota depletion caused significant defects in the early innate response to lung infection by the major human pathogen Klebsiella pneumoniae. After microbiota depletion, early clearance of K. pneumoniae was impaired, and this could be rescued by administration of bacterial Nod-like receptor (NLR) ligands (the NOD1 ligand MurNAcTri(DAP) and NOD2 ligand muramyl dipeptide [MDP]) but not bacterial Toll-like receptor (TLR) ligands. Importantly, NLR ligands from the gastrointestinal, but not upper respiratory, tract rescued host defenses in the lung. Defects in early innate immunity were found to be due to reduced reactive oxygen species-mediated killing of bacteria by alveolar macrophages. These data show that bacterial signals from the intestine have a profound influence on establishing the levels of antibacterial defenses in distal tissues.

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Authors: Clarke, T. B.
Affiliations: Imperial College London (GB)
Corresponding author: Clarke, Thomas B.
ORCID: Clarke, Thomas B.
Venue: Infection and Immunity
Publisher: American Society for Microbiology
Published: 2014-11
Volume: 82
Issue: 11
Pages: 4596-4606
ISSN: 0019-9567 (ISSN-L)
1098-5522
DOI: 10.1128/iai.02212-14
PMC: PMC4249320
OpenAlex: W2122379614
Cited by: 189
References: 69
Citations by year: 2026: 5 · 2025: 6 · 2024: 10 · 2023: 28 · 2022: 23 · 2021: 19 · 2020: 22 · 2019: 15 · 2018: 18 · 2017: 19 · 2016: 12 · 2015: 10 · 2014: 1
FWCI: 6.40
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Infection and Immunity (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Medical Research Council (MR/J006874/1)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords: commensal microbiota, innate immunity, pulmonary infection, Klebsiella pneumoniae, NOD1, NOD2, muramyl dipeptide, Toll-like receptor ligands, alveolar macrophages, reactive oxygen species, microbiota depletion
MeSH terms: Acetylmuramyl-Alanyl-Isoglutamine, Animals, Gene Expression Regulation, Immunity, Innate, Intestines, Klebsiella Infections, Klebsiella pneumoniae, Ligands, Lung Diseases, Mice, Inbred C57BL, Symbiosis, Macrophages, Alveolar, Reactive Oxygen Species, Mice, Nod Signaling Adaptor Proteins

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Early Innate Immunity to Bacterial Infection in the Lung Is Regulated Systemically by the Commensal Microbiota via Nod-Like Receptor Ligands

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