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

Madhulika Jupelli, M. Neal Guentzel, Patricia A. Meier, Guangming Zhong, Ashlesh K. Murthy, Bernard P. Arulanandam

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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-γ, not IL-4, production. Additionally, elevated IFN-γ, 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-γ or IFN-γ 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-γ production, and that endogenous IFN-γ is important in protection against this infection. The enhanced IFN-γ induction in the immature neo natal lung also may be relevant to the development of respiratory sequelae in adult life.

Original languageEnglish (US)
Pages (from-to)4148-4155
Number of pages8
JournalJournal of Immunology
Volume180
Issue number6
DOIs
StatePublished - Mar 15 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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