The intestinal microbiota are necessary for stressor-induced enhancement of splenic macrophage microbicidal activity

Allen, Rebecca G.; Lafuse, William P.; Galley, Jeffrey D.; Ali, Mohamed M.; Ahmer, Brian M.M.; Bailey, Michael T.

doi:10.1016/j.bbi.2011.11.002

Cited by 55Gut microbiota and healthImmune Response and InflammationStress Responses and Cortisol

The intestinal microbiota are necessary for stressor-induced enhancement of splenic macrophage microbicidal activity

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Allen, Rebecca G., Lafuse, William P., Galley, Jeffrey D., Ali, Mohamed M., Ahmer, Brian M.M., Bailey, Michael T.·2012·Brain Behavior and Immunity

DOI 10.1016/j.bbi.2011.11.002PMC PMC3288745

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Abstract

The indigenous microbiota impact mucosal, as well as systemic, immune responses, but whether the microbiota are involved in stressor-induced immunomodulation has not been thoroughly tested. A well characterized murine stressor, called social disruption (SDR), was used to study whether the microbiota are involved in stressor-induced enhancement of macrophage reactivity. Exposure to the SDR Stressor enhanced the ability of splenic macrophages to produce microbicidal mediators (e.g., inducible nitric oxide synthase (iNOS), superoxide anion, and peroxynitrite) and to kill target Escherichia coli. Exposure to the SDR Stressor also increased cytokine production by LPS-stimulated splenic macrophages. These effects, however, were impacted by the microbiota. Microbicidal activity and cytokine mRNA in splenic macrophages from Swiss Webster germfree mice that lack any commensal microbiota were not enhanced by exposure to the SDR Stressor. However, when germfree mice were conventionalized by colonizing them with microbiota from CD1 conventional donor mice, exposure to the SDR Stressor again increased microbicidal activity and cytokine mRNA. In follow-up experiments, immunocompetent conventional CD1 mice were treated with a cocktail of antibiotics to disrupt the intestinal microbiota. While exposure to the SDR Stressor-enhanced splenic macrophage microbicidal activity and cytokine production in vehicle-treated mice, treatment with antibiotics attenuated the SDR Stressor-induced increases in splenic macrophage reactivity. Treatment with antibiotics also prevented the stressor-induced increase in circulating levels of bacterial peptidoglycan, suggesting that translocation of microbiota-derived peptidoglycan into the body primes the innate immune system for enhanced activity. This study demonstrates that the microbiota play a crucial role in stressor-induced immunoenhancement.

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The gut microbiota is necessary for stress-induced immunomodulation, with enhancement of splenic macrophage reactivity occurring in colonized controls but not in germ-free mice in response to social disruption stress.
“A study by Allen et al. demonstrated that the GM is necessary for stress-induced immunomodulation, with enhancement of splenic macrophage reactivity occurring in colonized controls but not in germ-free mice, in response to social disruption stress (360).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [360]

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Authors: Allen, R. G., Lafuse, W. P., Galley, J. D., Ali, M. M., Ahmer, B. M. M., & Bailey, M. T.
Affiliations: The Ohio State University (US)
Corresponding author: Bailey, Michael T.
ORCID: Lafuse, William P.
Galley, Jeffrey D.
Ali, Mohamed M.
Ahmer, Brian M.M.
Bailey, Michael T.
Venue: Brain Behavior and Immunity
Publisher: Elsevier BV
Published: 2012-03
Volume: 26
Issue: 3
Pages: 371-382
ISSN: 0889-1591 (ISSN-L)
DOI: 10.1016/j.bbi.2011.11.002
PMC: PMC3288745
OpenAlex: W2040951062
Cited by: 55
References: 57
Citations by year: 2026: 1 · 2025: 2 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 5 · 2016: 7 · 2015: 3 · 2014: 5 · 2013: 4 · 2012: 6
FWCI: 1.95
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Brain Behavior and Immunity (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (RO3AI069097-01A1)
Ohio State University (RO1AI073971)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: gut microbiota, social stress, splenic macrophages, microbicidal activity, germ-free mice, antibiotic-induced microbiota depletion, inducible nitric oxide synthase, superoxide, peroxynitrite, cytokine production, innate immunity, Escherichia coli killing
MeSH terms: Animals, Escherichia coli, Intestines, Macrophage Activation, Macrophages, Spleen, Stress, Psychological, Superoxides, Cytokines, Immunity, Mucosal, Peroxynitrous Acid, Mice, Nitric Oxide Synthase Type II, Metagenome, Immunomodulation

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The intestinal microbiota are necessary for stressor-induced enhancement of splenic macrophage microbicidal activity

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