Infection and cellular defense dynamics in a novel 17β-estradiol murine model of chronic human group B streptococcus genital tract colonization reveal a role for hemolysin in persistence and neutrophil accumulation.
Genital tract carriage of group B streptococcus (GBS) is prevalent among adult women; however, the dynamics of chronic GBS genital tract carriage, including how GBS persists in this immunologically active host niche long term, are not well defined. To our knowledge, in this study, we report the first animal model of chronic GBS genital tract colonization using female mice synchronized into estrus by delivery of 17β-estradiol prior to intravaginal challenge with wild-type GBS 874391. Cervicovaginal swabs, which were used to measure bacterial persistence, showed that GBS colonized the vaginal mucosa of mice at high numbers (10(6)-10(7) CFU/swab) for at least 90 d. Cellular and histological analyses showed that chronic GBS colonization of the murine genital tract caused significant lymphocyte and PMN cell infiltrates, which were localized to the vaginal mucosal surface. Long-term colonization was independent of regular hormone cycling. Immunological analyses of 23 soluble proteins related to chemotaxis and inflammation showed that the host response to GBS in the genital tract comprised markers of innate immune activation including cytokines such as GM-CSF and TNF-α. A nonhemolytic isogenic mutant of GBS 874391, Δcyle9, was impaired for colonization and was associated with amplified local PMN responses. Induction of DNA neutrophil extracellular traps, which was observed in GBS-infected human PMNs in vitro in a hemolysin-dependent manner, appeared to be part of this response. Overall, this study defines key infection dynamics in a novel murine model of chronic GBS genital tract colonization and establishes previously unknown cellular and soluble defense responses to GBS in the female genital tract.
School of Medical Sciences, Griffith Health Institute, Griffith University, Gold Coast, Queensland 4222, Australia;
Alison J
AJ
Carey
Chee Keong
CK
Tan
Shaper
S
Mirza
Helen
H
Irving-Rodgers
Richard I
RI
Webb
Alfred
A
Lam
Glen C
GC
Ulett
D000818:Animals; D015415:Biomarkers; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004958:Estradiol / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006460:Hemolysin Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D060737:Reproductive Tract Infections / Q000276:immunology* / Q000382:microbiology; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014621:Vagina / Q000276:immunology* / Q000382:microbiology
D015415:Biomarkers; D016207:Cytokines; D006460:Hemolysin Proteins; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor