Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/112704
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Type: Journal article
Title: Infection and cellular defense dynamics in a novel 17 β-estradiol murine model of chronic human group B streptococcus genital tract colonization reveal a role for hemolysin in persistence and neutrophil accumulation
Other Titles: Infection and cellular defense dynamics in a novel 17 beta-estradiol murine model of chronic human group B streptococcus genital tract colonization reveal a role for hemolysin in persistence and neutrophil accumulation
Author: Carey, A.
Tan, C.
Mirza, S.
Irving-Rodgers, H.
Webb, R.
Lam, A.
Ulett, G.
Citation: Journal of Immunology, 2014; 192(4):1718-1731
Publisher: American Association of Immunologists
Issue Date: 2014
ISSN: 0022-1767
1550-6606
Statement of
Responsibility: 
Alison J. Carey, Chee Keong Tan, Shaper Mirza, Helen Irving-Rodgers, Richard I. Webb, x Alfred Lam, and Glen C. Ulett
Abstract: 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 (10⁶-10⁷ 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.
Keywords: Neutrophils
Description: Prepublished online 22 January 2014
Rights: Copyright © 2014 by The American Association of Immunologists, Inc.
RMID: 0030090070
DOI: 10.4049/jimmunol.1202811
Grant ID: http://purl.org/au-research/grants/arc/FT110101048
http://purl.org/au-research/grants/nhmrc/1052464
Appears in Collections:Obstetrics and Gynaecology publications

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