Endogenous IFN-γ 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-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 neonatal lung also may be relevant to the development of respiratory sequelae in adult life.

Heat denatured enzymatically inactive recombinant chlamydial protease-like activity factor induces robust protective immunity against genital chlamydial challenge

“…Chlamydial stocks were prepared as described previously [20, 21]. Confluent monolayers of HeLa cells were grown in Dulbecco’s modification of Eagle’s medium with 10% FBS and infected with Chlamydia muridarum.…”

Yersinia enterocoliticaPromotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates

“…For the first time, we demonstrate the development of both high T h 1 and T h 17 function in the neonatal intestine to a fully virulent infectious bacterium in the absence of additional interventions. Based on the current understanding that immune responsiveness during the neonatal period of life can be modulated extensively by targeting the mucosal immune system (1,8,11,12,27,29,34,35,59,70) and by using strong immunomodulatory agents (31,36,51), we favor the idea that robust immunity to Y. enterocolitica is a function of both the inflammatory potential of this pathogen and an intrinsic capacity of the neonatal intestine to develop high-level inflammation. These data support the idea that the development of inflammatory CD4…”

Neonatal chlamydial pneumonia induces altered respiratory structure and function lasting into adult life

“…Quasi-Static P-V Curves in Juveniles or Adult Mice Challenged With C. mur As pulmonary chlamydial infection leads to both peribronchiolar and interstitial inflammation, 14 quasi-static P-V loops were assessed to evaluate incremental lung volumes at Neonatal chlamydial pneumonia induced respiratory sequelae M Jupelli et al 5 or 8 weeks of age in mice challenged on D1 or D7 ( Figure 2). As seen in Figure 2, mice challenged with C. mur on D1 or D7 after birth displayed greater lung volumes at both 5 and 8 weeks of age than the corresponding mock (PBS)-challenged mice across the examined pressure range, with significant differences in maximal lung volumes at the greatest examined pressure (33 cm of H 2 O).…”