Examination of the Role of Secretory Leukocyte Protease Inhibitor (SLPI) During Gonococcal Infection
Abstract
Neisseria gonorrhoeae is a human-restricted pathogen that has evolved several mechanisms to evade host innate defenses. Secretory leukocyte protease inhibitor (SLPI) is an antimicrobial and anti-inflammatory peptide present in mucosal secretions. Here we show that wild-type N. gonorrhoeae strains are differentially susceptible to SLPI in vitro. The observed strain variability could not be explained by differences in the expression of the phase-variable opacity proteins as suggested by a recent study, or by differences in the expression of the MtrCDE active efflux pump, which expels other antimicrobial peptides. To further examine the interplay between N. gonorrhoeae and SLPI and to test the relevance of SLPI during gonococcal infection in vivo, we measured expression of SLPI in experimentally infected female mice via qRT-PCR and ELISA and studied the impact of SLPI on gonococcal colonization in SLPI-deficient mice. In BALB/c mice, increased SLPI expression occurred on day 1 of infection, followed by down-regulation at time points that coincided with a neutrophil influx. Strikingly, infected C57BL/6 mice, which do not mount a pro-inflammatory response to N. gonorrhoeae, showed increased SLPI expression that was sustained over time. This differential expression pattern however, did not occur at the protein level, as the concentration of SLPI in vaginal lavages remained constant despite the presence of infection or inflammation. Furthermore, SLPI-deficient mice cleared infection similarly to wild-type mice, suggesting that, despite being susceptible to SLPI in vitro, N. gonorrhoeae has the ability to protect against SLPI bactericidal activity in vivo. The analysis of a pro-inflammatory cytokine panel in SLPI-deficient mice revealed no differences in the inflammatory response to gonococcal infection compared to wild-type mice. Taken together, the results of this dissertation work indicate that SLPI is bactericidal against the gonococcus in vitro, but its ef
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 02, 2014
- Accession Number
- AD1127827
Entities
People
- Anita Marinelli
Organizations
- Uniformed Services University of the Health Sciences