The Duration of Chlamydia muridarum Genital Tract Infection and Associated Chronic Pathological Changes Are Reduced in IL-17 Knockout Mice but Protection Is Not Increased Further by Immunization

D W Andrew; M Cochrane; J H Schripsema; K H Ramsey; S J Dando; C P O'Meara; Peter Timms; K W Beagley

doi:10.1371/journal.pone.0076664

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The Duration of Chlamydia muridarum Genital Tract Infection and Associated Chronic Pathological Changes Are Reduced in IL-17 Knockout Mice but Protection Is Not Increased Further by Immunization

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The Duration of Chlamydia muridarum Genital Tract Infection and Associated Chronic Pathological Changes Are Reduced in IL-17 Knockout Mice but Protection Is Not Increased Further by Immunization

D W Andrew, M Cochrane, J H Schripsema, K H Ramsey, S J Dando, C P O'Meara, Peter Timms and K W Beagley

PLoS One, Vol.8(9), e7664

2013

DOI: https://doi.org/10.1371/journal.pone.0076664

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Abstract

Chlamydia

IL-17 is believed to be important for protection against extracellular pathogens, where clearance is dependent on neutrophil recruitment and local activation of epithelial cell defences. However, the role of IL-17 in protection against intracellular pathogens such as Chlamydia is less clear. We have compared (i) the course of natural genital tract C. muridarum infection, (ii) the development of oviduct pathology and (iii) the development of vaccine-induced immunity against infection in wild type (WT) BALB/c and IL-17 knockout mice (IL-17-/-) to determine if IL-17-mediated immunity is implicated in the development of infection-induced pathology and/or protection. Both the magnitude and duration of genital infection was significantly reduced in IL-17-/- mice compared to BALB/c. Similarly, hydrosalpinx was also greatly reduced in IL-17-/- mice and this correlated with reduced neutrophil and macrophage infiltration of oviduct tissues. Matrix metalloproteinase (MMP) 9 and MMP2 were increased in WT oviducts compared to IL-17-/- animals at day 7 post-infection. In contrast, oviducts from IL-17-/- mice contained higher MMP9 and MMP2 at day 21. Infection also elicited higher levels of Chlamydia-neutralizing antibody in serum of IL-17-/- mice than WT mice. Following intranasal immunization with C. muridarum Major Outer Membrane Protein (MOMP) and cholera toxin plus CpG adjuvants, significantly higher levels of chlamydial MOMP-specific IgG and IgA were found in serum and vaginal washes of IL-17-/- mice. T cell proliferation and IFNγ production by splenocytes was greater in WT animals following in vitro re-stimulation, however vaccination was only effective at reducing infection in WT, not IL-17-/- mice. Intranasal or transcutaneous immunization protected WT but not IL-17-/- mice against hydrosalpinx development. Our data show that in the absence of IL-17, the severity of C. muridarum genital infection and associated oviduct pathology are significantly attenuated, however neither infection or pathology can be reduced further by vaccination protocols that effectively protect WT mice. © 2013 Andrew et al.

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Title: The Duration of Chlamydia muridarum Genital Tract Infection and Associated Chronic Pathological Changes Are Reduced in IL-17 Knockout Mice but Protection Is Not Increased Further by Immunization
Authors: D W Andrew (Author) - Queensland University of Technology
M Cochrane (Author) - Queensland University of Technology
J H Schripsema (Author) - Midwestern University, United States
K H Ramsey (Author) - Midwestern University, United States
S J Dando (Author) - Queensland University of Technology
C P O'Meara (Author) - Queensland University of Technology
Peter Timms (Author) - Queensland University of Technology
K W Beagley (Author) - Queensland University of Technology
Publication details: PLoS One, Vol.8(9), e7664; 14
Publisher: Public Library of Science
Date published: 2013
DOI: 10.1371/journal.pone.0076664
ISSN: 1932-6203
Copyright note: Copyright © 2013 Andrew et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Organisation Unit: University of the Sunshine Coast, Queensland; Centre for Bioinnovation
Language: English
Record Identifier: 99448825802621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Immunology

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