title: Endogenous IFN-gamma production is induced and required for protective immunity against pulmonary chlamydial infection in neonatal mice.
abstract: Chlamydia trachomatis infection in neonates, not adults, has been associated with the development of chronic respiratory sequelae. Adult chlamydial infections induce Th1-type responses that subsequently clear the infection, whereas the neonatal immune milieu in general has been reported to be biased toward Th2-type responses. We examined the protective immune responses against intranasal Chlamydia muridarum challenge in 1-day-old C57BL/6 and BALB/c mice. Infected C57BL/6 pups displayed earlier chlamydial clearance (day 14) compared with BALB/c pups (day 21). However, challenged C57BL/6 pups exhibited prolonged deficits in body weight gain (days 12-30) compared with BALB/c pups (days 9-12), which correlated with continual pulmonary cellular infiltration. Both strains exhibited a robust Th1-type response, including elevated titers of serum antichlamydial IgG2a and IgG2b, not IgG1, and elevated levels of splenic C. muridarum-specific IFN-gamma, not IL-4, production. Additionally, elevated IFN-gamma, not IL-4 expression, was observed locally in the infected lungs of both mouse strains. The immune responses in C57BL/6 pups were significantly greater compared with BALB/c pups after chlamydial challenge. Importantly, infected mice deficient in IFN-gamma or IFN-gamma receptor demonstrated enhanced chlamydial dissemination, and 100% of animals died by 2 wk postchallenge. Collectively, these results indicate that neonatal pulmonary chlamydial infection induces a robust Th1-type response, with elevated pulmonary IFN-gamma production, and that endogenous IFN-gamma is important in protection against this infection. The enhanced IFN-gamma induction in the immature neonatal lung also may be relevant to the development of respiratory sequelae in adult life.
authors.affiliation: South Texas Center for Emerging Infectious Diseases, Department of Biology, University of Texas, San Antonio, TX 78249, USA.
authors.forename: Madhulika
authors.initials: M
authors.lastname: Jupelli
authors.forename: M Neal
authors.initials: MN
authors.lastname: Guentzel
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Meier
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
authors.forename: Ashlesh K
authors.initials: AK
authors.lastname: Murthy
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Arulanandam
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000276:immunology; D002690:Chlamydia Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D023502:Chlamydia muridarum / Q000276:immunology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007110:Immunity, Active / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
chemical_list: D007371:Interferon-gamma