Interleukin-17A Contributes to the Control of Streptococcus pyogenes Colonization and Inflammation of the Female Genital Tract.

Alison J Carey,Suzanne R Dawid,Victor Nizet,Jason B Weinberg,Michael G Caparon,Michael E Watson,Mark J Walker,Carola Venturini,Glen C Ulett,Alfred K Lam

doi:10.1038/srep26836

Abstract

Postpartum women are at increased risk of developing puerperal sepsis caused by group A Streptococcus (GAS). Specific GAS serotypes, including M1 and M28, are more commonly associated with puerperal sepsis. However, the mechanisms of GAS genital tract infection are not well understood. We utilized a murine genital tract carriage model to demonstrate that M1 and M28 GAS colonization triggers TNF-α, IL-1β, and IL-17A production in the female genital tract. GAS-induced IL-17A significantly influences streptococcal carriage and alters local inflammatory responses in two genetically distinct inbred strains of mice. An absence of IL-17A or the IL-1 receptor was associated with reduced neutrophil recruitment to the site of infection; and clearance of GAS was significantly attenuated in IL-17A−/− mice and Rag1−/− mice (that lack mature lymphocytes) but not in mice deficient for the IL-1 receptor. Together, these findings support a role for IL-17A in contributing to the control of streptococcal mucosal colonization and provide new insight into the inflammatory mediators regulating host-pathogen interactions in the female genital tract.

Highlights

Streptococcus pyogenes is an obligate human pathogen causing mild active inflammation of the skin and throat, or severe infection when invading sterile sites of the body[1,2]
We find that group A Streptococcus (GAS) cervico-vaginal infection triggers host inflammation at the cellular and soluble level, with host IL-17A playing an important role in successful clearance of streptococcal mucosal infection
In mice treated with estradiol only at the initiation of infection, M28 GAS was recovered from the vaginal vault at levels of 105–106 colony-forming units (CFU)/swab for the first two to three weeks following challenge; colonization persisted for at least 30 days the M28 GAS strain was eventually cleared from the mucosa (Fig. 1)

Summary

Introduction

Streptococcus pyogenes (group A Streptococcus; GAS) is an obligate human pathogen causing mild active inflammation of the skin and throat, or severe infection when invading sterile sites of the body[1,2]. GAS can penetrate deeper body tissues following pharyngeal or epidermal colonization, and via proliferation in the mucosal tissues of the female urogenital tract. It is recognized as a significant etiologic agent of puerperal sepsis[6,7,8]. The role of IL-17A in response to GAS urogenital tract infection has not been previously addressed due to lack of a suitable animal model. Murine models of cervico-vaginal colonization suitable for the study of urogenital GAS and group B Streptococcus (GBS) infection have been reported[22,23]. We find that GAS cervico-vaginal infection triggers host inflammation at the cellular and soluble level, with host IL-17A playing an important role in successful clearance of streptococcal mucosal infection

Methods

Results

Conclusion