Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response.
Most cystic fibrosis (CF) patients become chronically infected with Pseudomonas aeruginosa in the lungs. The infection is characterized by a pronounced antibody response and a persistant inflammation dominated by polymorphonuclear neutrophils. Moreover a high antibody response correlates with a poor prognosis. We speculated that a change from this Th2-like response to a Th1-like response might decrease the lung inflammation and thus improve the prognosis in CF patients. To investigate this, we infected C3H/HeN and BALB/c mice intratracheally with P. aeruginosa. In addition, we studied the early 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<0.01, day 7 p<0.02), had a milder lung inflammation (day 7 p<0.01, day 14 p< or =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/IL-12 ratio (p< or =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, indicating that a Th1 response might be beneficial in CF patients with chronic P. aeruginosa lung infection.
Moser
C
C
Department of Clinical Microbiology, Rigshospitalet, Copenhagen Denmark.
Hougen
H P
HP
Song
Z
Z
Rygaard
J
J
Kharazmi
A
A
Høiby
N
N
D000818:Animals; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009569:Nitric Oxide / Q000096:biosynthesis; D018410:Pneumonia, Bacterial / Q000150:complications / Q000276:immunology*; D011379:Prognosis; D011552:Pseudomonas Infections / Q000150:complications / Q000276:immunology*; D013045:Species Specificity; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D007074:Immunoglobulin G; D009569:Nitric Oxide