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.
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. muridarumMajor 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.
Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
Dean W
DW
Andrew
Melanie
M
Cochrane
Justin H
JH
Schripsema
Kyle H
KH
Ramsey
Samantha J
SJ
Dando
Connor P
CP
O'Meara
Peter
P
Timms
Kenneth W
KW
Beagley
D000281:Administration, Intranasal; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D023502:Chlamydia muridarum / Q000472:pathogenicity*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D010057:Oviducts / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D060737:Reproductive Tract Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D013997:Time Factors; D014621:Vagina / Q000187:drug effects / Q000276:immunology / Q000473:pathology
D001428:Bacterial Vaccines; D016207:Cytokines; D020381:Interleukin-17; D007371:Interferon-gamma; D020782:Matrix Metalloproteinases