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Updated: May 15, 2025
An Intestinal Gut Organ Culture System for Analyzing Host-Microbiota Interactions
Published on: June 30, 2021
Sex-dependent gastrointestinal colonization resistance to MRSA is microbiota and Th17 dependent
Alannah Lejeune1,2, Chunyi Zhou1,2, Defne Ercelen3
1Department of Microbiology, New York University School of Medicine, New York, United States.
Abstract:
Gastrointestinal (GI) colonization by methicillin-resistant Staphylococcus aureus (MRSA) is associated with a high risk of transmission and invasive disease in vulnerable populations. The immune and microbial factors that permit GI colonization remain unknown. Male sex is correlated with enhanced Staphylococcus aureus nasal carriage, skin and soft tissue infections, and bacterial sepsis. Here, we established a mouse model of sexual dimorphism during GI colonization by MRSA. Our results show that in contrast to male mice that were susceptible to persistent colonization, female mice rapidly cleared MRSA from the GI tract following oral inoculation in a manner dependent on the gut microbiota. This colonization resistance displayed by female mice was mediated by an increase in IL-17A+ CD4+ T cells (Th17) and dependent on neutrophils. Ovariectomy of female mice increased MRSA burden, but gonadal female mice that have the Y chromosome retained enhanced Th17 responses and colonization resistance. Our study reveals a novel intersection between sex and gut microbiota underlying colonization resistance against a major widespread pathogen.
Insights
Female mice resist gastrointestinal colonization by methicillin-resistant Staphylococcus aureus (MRSA) due to gut microbiota and enhanced Th17 immune responses. This sex-based difference highlights a novel interaction between host immunity and the microbiome in pathogen resistance.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Gastrointestinal (GI) colonization by methicillin-resistant Staphylococcus aureus (MRSA) poses significant transmission and invasive disease risks.
- Factors governing GI MRSA colonization, particularly sex-based differences, are not well understood.
- Male sex is linked to increased Staphylococcus aureus infections and carriage.
Purpose of the Study:
- To investigate sexual dimorphism in GI colonization by MRSA using a mouse model.
- To elucidate the immune and microbial mechanisms underlying sex-based differences in MRSA colonization resistance.
Main Methods:
- Establishment of a mouse model to study GI MRSA colonization with a focus on sex differences.
- Assessment of MRSA clearance in male and female mice following oral inoculation.
- Analysis of immune cell populations (Th17) and neutrophil involvement.
- Evaluation of the impact of ovariectomy and gonadal status on colonization.
Main Results:
- Female mice demonstrated rapid clearance of GI MRSA, while male mice exhibited persistent colonization.
- Colonization resistance in females was dependent on the gut microbiota.
- Enhanced IL-17A+ CD4+ T cell (Th17) responses and neutrophils mediated resistance in females.
- Ovariectomy diminished colonization resistance in females, while gonadal status influenced Th17 responses.
Conclusions:
- A significant sexual dimorphism exists in GI colonization resistance against MRSA.
- Gut microbiota and Th17-mediated immunity play crucial roles in conferring colonization resistance in females.
- This study uncovers a novel interplay between sex, gut microbiota, and immunity in controlling MRSA colonization.
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