Journal article
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
The Journal of immunology (1950), Vol.192(4), pp.1718-1731
15 Feb 2014
PMID: 24453257
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 17 beta-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-alpha. A nonhemolytic isogenic mutant of GBS 874391, triangle cyle9, 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.
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Details
- Title
- 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
- Creators
- Alison J. Carey - Griffith UniversityChee Keong Tan - Griffith UniversityShaper Mirza - University of Texas at BrownsvilleHelen Irving-Rodgers - Queensland University of TechnologyRichard I. Webb - University of QueenslandAlfred Lam - Griffith UniversityGlen C. Ulett - Griffith University
- Publication Details
- The Journal of immunology (1950), Vol.192(4), pp.1718-1731
- Publisher
- American Association of Immunologists
- Number of pages
- 14
- Grant note
- APP1052464 / National Health and Medical Research Council Peter Doherty Australian Biomedical Fellowship; National Health and Medical Research Council (NHMRC) of Australia Discovery Early Career Researcher Award from the Australian Research Council; Australian Research Council FT110101048 / Future Fellowship from the Australian Research Council; Australian Research Council Prime Minister's Endeavor Asia Fellow Early Career Researcher grant from the Griffith Health Institute
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University; Pediatrics; College of Medicine
- Identifiers
- 991020100069304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology