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Chronic Pseudomonas aeruginosa lung infection is more severe in Th2 responding BALB/c mice compared to Th1 responding
C Moser1, H K Johansen, Z Song
1Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
Abstract:
The chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) is characterized by a pronounced antibody response and microcolonies surrounded by numerous polymorphonuclear neutrophils (PMN). Poor prognosis is correlated with a high antibody response to P. aeruginosa antigens. An animal model of this infection was established in two strains of mice: C3H/HeN and BALB/c, generally known as Th1 and Th2 responders, respectively, which were challenged with alginate-embedded P. aeruginosa. Mortality was significantly lower in C3H/HeN compared to BALB/c mice (p < 0.025). P. aeruginosa was cleared more efficiently in C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology (p < 0.02), and we found significantly fewer microabscesses in C3H/HeN mice than in BALB/c mice (p < 0.005). In supernatants from P. aeruginosa antigen and concanavalin A-stimulated spleen cells from the two strains of mice, the interferon-(IFN-) gamma levels were higher, whereas IL-4 levels were lower in C3H/HeN mice than in BALB/c mice. The implications of these findings for CF patients with chronic P. aeruginosa lung infection are discussed.
Insights
Mice with a Th1 immune response showed better outcomes against Pseudomonas aeruginosa lung infections than Th2 responders. This suggests Th1 immunity may be protective in cystic fibrosis (CF) patients.
Area of Science:
- Immunology
- Microbiology
- Pulmonary Medicine
Background:
- Chronic Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients is linked to poor prognosis, characterized by high antibody responses and neutrophil presence.
- The immune response profile, specifically T-helper (Th) cell responses, may influence infection outcomes.
Purpose of the Study:
- To investigate the role of Th1 versus Th2 immune responses in an animal model of chronic Pseudomonas aeruginosa lung infection.
- To compare the efficacy of infection clearance and host response between Th1-prone (C3H/HeN) and Th2-prone (BALB/c) mice.
Main Methods:
- Establishment of a murine model using C3H/HeN and BALB/c mice challenged with alginate-embedded Pseudomonas aeruginosa.
- Assessment of mortality rates, bacterial clearance, lung histopathology (microabscesses), and cytokine profiles (interferon-gamma and IL-4) from stimulated spleen cells.
Main Results:
- C3H/HeN (Th1) mice exhibited significantly lower mortality (p < 0.025) and more efficient bacterial clearance compared to BALB/c (Th2) mice.
- Histopathological analysis revealed significantly better lung tissue preservation (p < 0.02) and fewer microabscesses (p < 0.005) in C3H/HeN mice.
- Spleen cells from C3H/HeN mice produced higher levels of interferon-gamma and lower levels of IL-4 upon stimulation, consistent with a Th1-biased response.
Conclusions:
- A Th1-dominant immune response is associated with better control and reduced pathology during chronic Pseudomonas aeruginosa lung infection in this murine model.
- These findings suggest that promoting a Th1 immune response could be a potential therapeutic strategy for managing chronic P. aeruginosa infections in cystic fibrosis patients.