Comparison of Bacterial Burden and Cytokine Gene Expression in Golden Hamsters in Early Phase of Infection with Two Different Strains of <i>Leptospira interrogans</i>

<div><p>Leptospirosis, a zoonotic infection with worldwide prevalence, is caused by pathogenic spirochaetes of <i>Leptospira</i> spp., and exhibits an extremely broad clinical spectrum in human patients. Although previous studies indicated that specific serovars or genotypes of <i>Leptospira</i> spp. were associated with severe leptospirosis or its outbreak, the mechanism underlying the difference in virulence of the various <i>Leptospira</i> serotypes or genotypes remains unclear. The present study addresses this question by measuring and comparing bacterial burden and cytokine gene expression in hamsters infected with strains of two <i>L</i>. <i>interrogans</i> serovars Manilae (highly virulent) and Hebdomadis (less virulent). The histopathology of kidney, liver, and lung tissues was also investigated in infected hamsters. A significantly higher bacterial burden was observed in liver tissues of hamsters infected with serovar Manilae than those infected with serovar Hebdomadis (p < 0.01). The average copy number of the leptospiral genome was 1,302 and 20,559 in blood and liver, respectively, of hamsters infected with serovar Manilae and 1,340 and 4,896, respectively, in hamsters infected with serovar Hebdomadis. The expression levels of <i>mip1alpha</i> in blood; <i>tgfbeta</i>, <i>il1beta</i>, <i>mip1alpha</i>, <i>il10</i>, <i>tnfalpha</i> and <i>cox2</i> in liver; and <i>tgfbeta</i>, <i>il6</i>, <i>tnfalpha</i> and <i>cox2</i> in lung tissue were significantly higher in hamsters infected with serovar Manilae than those infected with serovar Hebdomadis (p < 0.05). In addition, infection with serovar Manilae resulted in a significantly larger number of hamsters with <i>tnfalpha</i> upregulation (p = 0.04). Severe distortion of tubular cell arrangement and disruption of renal tubules in kidney tissues and hemorrhage in lung tissues were observed in Manilae-infected hamsters. These results demonstrate that serovar Manilae multiplied more efficiently in liver tissues and induced significantly higher expression of genes encoding pro- and anti-inflammatory cytokines than serovar Hebdomadis even in tissues for which a significant difference in leptospiral load was not observed. In addition, our results suggest a serovar Manilae-specific mechanism responsible for inducing severe damage in kidneys and hemorrhage in lung.</p>