[Neutralization of interleukin-17 aggravates respiratory infection induced by Chlamydia trachomatis in mice].

Objective: To evaluate the role of interleukin-17 (IL-17) in respiratory infection with Chlamydia trachomatis in mice.

Methods: (1) In the study, 32 mice were randomly divided into the following 4 groups (8 mice/group): neutralizing antibody group (NG), isotype-matched control antibody group (IG), compensating recombinant mouse IL-17 group (CG) and PBS control group (PG), respectively. The mice in all the groups were induced by intranasal inoculation with high dose of inclusion-forming unit (IFU) Chlamydia trachomatis mouse pneumonitis (MoPn). Meanwhile, they were injected intraperitoneally with neutralizing rat antimouse IL-17 mAb, or control rat IgG, or neutralizing rat antimouse IL-17 mAb plus recombinant mouse IL-17 or PBS alone every 48 h starting on day 1 before chlamydial infecton. The mice were monitored daily for body weight change and survival rates. (2) Another 32 mice were randomly divided into 4 groups as method (1),and intranasally infected with moderate dose of MoPn, and the following steps were taken as the same as method (1). The bronchial alveolar lavage fluids (BALF) were collected for counting neutrophils, macrophages, and lymphocytes on day 8 postinfection. At the same time, the chlamydial growth in the lung, kidney and spleen were assessed by inoculating HeLa cell monolayer with homogenates followed by immunofluoresent assay (IFA).

Results: After being infected by high dose of MoPn and neutralized with anti-IL-17 mAb, the average body weight change decreased obviously in all the groups and began to increase 12 d after infection in IG, CG and PG, but only the mice in NG continued to lose their body weight till all died. The survival rate of the mice decreased significantly in NG and all died on day 21 postinfection. There were significant differences compared with IG, CG and PG groups (χ(2)= 11.096,10.575,13.781, respectively, P<0.05). But the survival rates of the mice were 75%, 75% and 87.5% for IG, CG and PG respectively, and there were no significant differences among the three groups. After being infected by moderate dose of MoPn, the chlymadia growth in the lung and the spread to the kidney and spleen significantly increased in NG (6.85±0.12, 1.85±0.35, and 1.59±0.35, P<0.05), compared with IG (6.03±0.25, 0.86±0.80, 0.57±0.42), CG (5.42±0.66, 0.43±0.23, 0.21±0.15) and PG (5.65±0.29, 0.68±0.39, but not detected in the spleen), these data were expressed as lg IFUs/organ. The results of BALF cell differentials were calculated as the percentage of the total cells and the final results of neutrophils, macrophages, and lymphocytes were 54.17%±5.29%, 26.92%±6.28%, 18.90%±5.01% for NG, 74.50%±7.33%, 13.43%±5.69%, 12.06%±6.64% for IG, 76.13%±8.12%, 12.31%±7.73%, 11.56%±7.25% for CG, and 69.97%±6.45%, 14.55%±6.59%, and 15.48%±6.11% for PG. The ratios of neutrophils, macrophages, and lymphocytes in BALF of NG had significant differences compared with the other groups (P<0.001). The neutrophil population in the BALF was significantly decreased in NG than that of the other groups.

Conclusion: After the endogenous IL-17 activity had been neutralized, the mice showed greater body weight loss, less survival rate, higher bacterial growth in the lung and more spread to other organs, and less neutrophils inflitration. These data suggest that IL-17 plays a critical protective role in the host defense against chlamydial infection.