IL-10 Deficiency Protects Hamsters from Leptospira Infection

Abstract

Leptospirosis is a global zoonotic disease with outcomes ranging from subclinical infection to fatal Weil's syndrome. In addition to antibiotics, some immune activators have shown protective effects against leptospirosis. However, the unclear relationship between Leptospira and cytokines has limited the development of antileptospiral immunomodulators. In this study, the particular role of interleukin-10 (IL-10) in leptospirosis was explored by using IL-10-defective (IL-10^-/-) hamsters. After Leptospira infection, an improved survival rate, reduced leptospiral burden, and alleviation of organ lesions were found in IL-10^-/- hamsters compared with wild-type (WT) hamsters. In addition, the levels of expression of the IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α) genes and the level of nitric oxide (NO) were higher in IL-10^-/- hamsters than in WT hamsters. Our results indicate that IL-10 deficiency protects hamsters from Leptospira infection.

Keywords: IL-10; hamster; inflammation; leptospirosis.

FIG 1

IL-10^−/− hamsters are more resistant to Leptospira infection than WT hamsters. (A) Survival curves of WT hamsters (n = 12) and IL-10^−/− hamsters (n = 12) intraperitoneally infected with 10⁶ leptospires. The animal experiment was repeated twice. *, P < 0.05 versus infected controls, as determined by a Kaplan-Meier log rank test. (B) Bacterial burdens in the kidneys, livers, and lungs of WT hamsters (n = 4) and IL-10^−/− hamsters (n = 4). Samples were collected at 4 days p.i. The results are presented as numbers of genome equivalents per microgram of tissue DNA, and the differences were compared by t test. *, P < 0.05.

FIG 2

IL-10 deficiency alleviates organ lesions. (A) Histopathology of kidneys (a and b), livers (c and d), and lungs (e and f) of WT and IL-10^−/− hamsters, respectively. Samples were collected at 4 days p.i. (100×; scale bar, 100 μm). (B to D) Histopathological scores for the kidneys (B), livers (C), and lungs (D) of WT hamsters (n = 6) and IL-10^−/− hamsters (n = 6) at 4 days p.i. Data are presented as means ± standard deviation (SD), and the differences were compared by the Wilcoxon rank sum test. *, P < 0.05; **, P < 0.01.

FIG 3

IL-10 deficiency elevates the level of expression of proinflammatory cytokine genes. (A to C) Expression of the TNF-α, IL-1β, and IL-6 genes in the kidneys of WT hamsters (n = 10) and IL-10^−/− hamsters (n = 10). (D to F) Expression of the TNF-α, IL-1β, and IL-6 genes in the livers of WT hamsters (n = 10) and IL-10^−/− hamsters (n = 10). (G to I) Expression of the TNF-α, IL-1β, and IL-6 genes in the lungs of WT hamsters (n = 10) and IL-10^−/− hamsters (n = 10). The results represent the relative expression in each sample after being normalized to the average from the WT hamsters. Samples were collected at 2 days p.i. Data are presented as the means ± SD from four independent experiments, and the differences were compared by t test. *, P < 0.05; **, P < 0.01; ns, not significant.

FIG 4

IL-10 deficiency increases the level of NO. Shown are the NO levels in the kidneys, livers, and lungs of WT hamsters (n = 10) and IL-10^−/− hamsters (n = 10). Samples were collected at 2 days p.i. Data are presented as the means ± SD from four independent experiments, and the differences were compared by t test. *, P < 0.05.