title: The recall response induced by genital challenge with Chlamydia muridarum protects the oviduct from pathology but not from reinfection.
abstract: The significant morbidities of ectopic pregnancy and infertility observed in women after Chlamydia trachomatis genital infection result from ascension of the bacteria from the endocervix to the oviduct, where an overly aggressive inflammatory response leads to chronic scarring and Fallopian tube obstruction. A vaccine to prevent chlamydia-induced disease is urgently needed. An important question for vaccine development is whether sterilizing immunity at the level of the oviduct is essential for protection because of the possibility that a chlamydial component drives a deleterious anamnestic T cell response upon oviduct reinfection. We show that mice inoculated with attenuated plasmid-cured strains of Chlamydia muridarum are protected from oviduct pathology upon challenge with wild-type C. muridarum Nigg despite induction of a response that did not prevent reinfection of the oviduct. Interestingly, repeated abbreviated infections with Nigg also elicited recall responses that protected the oviduct from pathology despite low-level reinfection of this vulnerable tissue site. Challenged mice displayed significant decreases in tissue infiltration of inflammatory leukocytes with marked reductions in frequencies of neutrophils but significant increases in frequencies of CD4 Th1 and CD8 T cells. An anamnestic antibody response was also detected. These data indicate that exposure to a live attenuated chlamydial vaccine or repeated abbreviated genital infection with virulent chlamydiae promotes anamnestic antibody and T cell responses that protect the oviduct from pathology despite a lack of sterilizing immunity at the site.
authors.affiliation: Children's Hospital of Pittsburgh, Department of Pediatrics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Riley
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Zurenski
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Frazer
authors.forename: Catherine M
authors.initials: CM
authors.lastname: O'Connell
authors.forename: Charles W
authors.initials: CW
authors.lastname: Andrews
authors.forename: Margaret
authors.initials: M
authors.lastname: Mintus
authors.forename: Toni
authors.initials: T
authors.lastname: Darville
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D023502:Chlamydia muridarum / Q000276:immunology*; D005260:Female; D005831:Genital Diseases, Female / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007249:Inflammation / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D010057:Oviducts / Q000166:cytology / Q000473:pathology*; D011247:Pregnancy; D018417:Th1 Cells / Q000502:physiology; D013997:Time Factors; D014613:Vaccines, Attenuated
chemical_list: D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated