Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response
C. Moser et al., Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response, APMIS, 107(12), 1999, pp. 1093-1100
Most cystic fibrosis (CF) patients become chronically infected with Pseudom
onas aeruginosa in the lungs. The infection is characterized by a pronounce
d antibody response and a persistant inflammation dominated by polymorphonu
clear neutrophils. Moreover a high antibody response correlates with a poor
prognosis. We speculated that a change from this Th2-like response to a Th
1-like response might decrease the lung inflammation and thus improve the p
rognosis in CF patients. To investigate this, we infected C3H/HeN and BALB/
c mice intratracheally with P. aeruginosa. In addition, we studied the earl
y immune response leading to different Th responses. Mortality was lower in
the C3H/ HeN mice (p<0.005), they cleared the bacteria faster (day 3 p<0.0
1, day 7 p<0.02), had a milder lung inflammation (day 7 p<0.01, day 14 p le
ss than or equal to 0.0005) and had a Th1-like IgG subclass switch. At day
3, the C3H/HeN mice produced less NO and TNF-alpha, (p<0.01 and p<0.03) and
had the lowest IL-10/IL12 ratio (p less than or equal to 0.05). At day 7,
the C3H/HeN mice had the highest IFN-gamma (p<0.02), and the lowest IL-4 (p
<0.02) production in the lungs. In conclusion, these results show that the
Th1-reacting C3H/ HeN mice with chronic P. aeruginosa lung infection have a
better disease outcome compared to the Th2-reacting BALB/c mice, indicatin
g that a Th1 response might be beneficial in CF patients with chronic P. ae
ruginosa lung infection.