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Staphylococcus aureus Colonization Induces Strain-Specific Suppression of Interleukin-17
Aylana Reiss-Mandel1,2, Carmit Rubin1, Morad Zayoud2,3
1Infectious Disease Unit, Sheba Medical Center, Ramat Gan, Israel.
Infection and Immunity
|January 10, 2018
Summary
Persistent Staphylococcus aureus carriage in individuals is linked to a suppressed immune response. Interleukin-19 (IL-19) plays a key role in this tolerogenic effect, influencing Th17 cell activity and potentially determining carriage patterns.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Staphylococcus aureus is a significant pathogen responsible for considerable illness and death.
- Nasal carriage of S. aureus is a primary route for transmission and endogenous infections, with persistent carriage affecting approximately 30% of healthy individuals.
- While T helper 17 (Th17) cells are implicated in S. aureus infection and clearance, the immune mechanisms underlying nasal carriage remain poorly understood.
Purpose of the Study:
- To investigate the Th17 immune response and its regulatory mechanisms during Staphylococcus aureus nasal carriage.
- To determine if the immune response differs between endogenous (carried) and exogenous (non-carried) S. aureus strains.
- To explore the role of IL-19 in modulating the Th17 response in the context of S. aureus carriage.
Main Methods:
- Recruitment of 25 volunteers, including 11 persistent S. aureus carriers.
- Stimulation of peripheral blood mononuclear cells (PBMCs) with endogenous or exogenous S. aureus strains.
- Measurement of Th17 cell frequency, IL-17 mRNA and protein levels using flow cytometry, real-time PCR, and ELISA.
- Assessment of IL-17 suppressors, including regulatory T cells (FOXP3), IL-10, IL-27, and IL-19.
Main Results:
- Th17 and IL-17 levels were significantly lower when PBMCs were stimulated with endogenous S. aureus strains compared to exogenous strains.
- Among the tested suppressive cytokines, only IL-19 showed a stronger response to endogenous strains.
- Addition of recombinant IL-19 reduced IL-17 expression in response to exogenous strains, while IL-19 antibodies increased IL-17 response to endogenous strains.
Conclusions:
- S. aureus carriage induces a tolerogenic immune response specific to the carried strain.
- IL-19 appears to be a key mediator of this tolerogenic response, suppressing IL-17 production.
- The differential immune response, potentially mediated by IL-19, may influence the persistence of S. aureus nasal carriage.
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