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Updated: Feb 10, 2026
Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Gut microbiota-driven IL-17A production by hepatic γδ T cells enhances neutrophil defense against systemic
Na Pan1,2, Xing Su1, Yifei Meng1
1Microbiology and Immunology Laboratory, School of Life Sciences, Inner Mongolia University, Hohhot, China.
Abstract:
Staphylococcus aureus (S. aureus) bloodstream infections pose a significant clinical threat, exacerbated by increasing antibiotic resistance and high mortality. While the gut microbiota is recognized as a key modulator of systemic immunity, the mechanisms underlying its protective role against invasive bacterial infections remain incompletely understood. Here, we investigated how gut microbiota influences hepatic immune responses during early S. aureus bloodstream infection using animal models. Our findings demonstrate that the gut microbiota exerts a protective effect against systemic S. aureus infection. Specifically, commensal microbiota-derived signals prime hepatic γδ T cells for rapid interleukin-17A (IL-17A) production upon bacterial challenge. This microbiota-dependent IL-17A response subsequently promotes neutrophil recruitment to the liver, facilitating bacterial clearance and limiting systemic dissemination. Disruption of the gut microbiota impaired hepatic γδ T cell IL-17A production, reduced neutrophil mobilization, and compromised host resistance to infection. Notably, we found that colonization with the commensal Limosilactobacillus reuteri (L. reuteri) activates this hepatic γδT17-neutrophil axis, enhancing host defense against S. aureus as a mechanism involving indole metabolites. This study reveals a novel gut-liver axis whereby intestinal microbiota orchestrates hepatic γδ T cell function to establish an early immunological barrier against invasive bacterial pathogens, offering potential therapeutic avenues for enhancing host defense against life-threatening S. aureus infections.
Insights
The gut microbiota protects against Staphylococcus aureus infections by priming liver immune cells. This process enhances neutrophil response, aiding bacterial clearance and improving host defense.
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Staphylococcus aureus bloodstream infections present a major clinical challenge due to rising antibiotic resistance and high mortality rates.
- The gut microbiota's role in modulating systemic immunity and protecting against invasive bacterial infections is recognized but not fully understood.
- Understanding the gut-liver axis in immunity is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate how the gut microbiota influences hepatic immune responses during early Staphylococcus aureus bloodstream infection.
- To elucidate the mechanisms by which gut commensals enhance host defense against invasive bacterial pathogens.
- To identify potential therapeutic targets for improving outcomes in S. aureus infections.
Main Methods:
- Utilized animal models to study hepatic immune responses to Staphylococcus aureus bloodstream infection.
- Analyzed the impact of gut microbiota composition on immune cell function, specifically hepatic γδ T cells and neutrophils.
- Investigated the role of specific commensal bacteria, Limosilactobacillus reuteri, and their metabolites in modulating host defense.
Main Results:
- Gut microbiota confers protection against systemic S. aureus infection.
- Commensal microbiota primes hepatic γδ T cells to produce IL-17A, promoting neutrophil recruitment to the liver for bacterial clearance.
- Disruption of gut microbiota impairs this immune axis, reducing host resistance; Limosilactobacillus reuteri enhances defense via indole metabolites.
Conclusions:
- A novel gut-liver immune axis exists where gut microbiota orchestrates hepatic γδ T cell function to combat invasive bacterial pathogens.
- This microbiota-dependent immune pathway establishes an early defense barrier against S. aureus.
- Targeting this gut-liver axis presents a promising therapeutic avenue for enhancing host defense against S. aureus infections.
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