Endogenous IFN-gamma production is induced and required for protective immunity against pulmonary chlamydial infection in neonatal mice

J Immunol. 2008 Mar 15;180(6):4148-55. doi: 10.4049/jimmunol.180.6.4148.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Intranasal
  • Animals
  • Animals, Newborn / growth & development
  • Animals, Newborn / immunology
  • Chlamydia Infections / immunology*
  • Chlamydia Infections / pathology
  • Chlamydia Infections / prevention & control*
  • Chlamydia muridarum / immunology*
  • Female
  • HeLa Cells
  • Humans
  • Immunity, Active / genetics
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Interferon-gamma / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pneumonia, Bacterial / immunology*
  • Pneumonia, Bacterial / pathology
  • Pneumonia, Bacterial / prevention & control*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1 Cells / microbiology


  • Interferon-gamma