TLR4 competence and mouse models of sublethal leptospirosis

Abstract

Mice are slowly being accepted as alternative models for investigation of leptospiral infection. The strain often used to analyze sublethal disease (C3H/HeJ) expresses a hyporesponsive tlr4 gene in its cells and thus the model is deemed immunocompromised. To help resolve this scientific concern we compared infection of mice expressing competent tlr4 (C3H/HeN, C57BL6) versus tlr4 hyporesponsive mice (C3H/ HeJ) with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 over a period of two weeks. We found that the two mouse strains with a functional tlr4 gene (C3H/HeN and C57BL/6) developed clinical and molecular signs of leptospirosis less pronounced but not significantly different than tlr4 hyporesponsive C3H/HeJ, as quantified by weight loss, survival curves, presence of Leptospira 16S rRNA in blood and urine and burden of viable spirochetes in kidney as compared to the respective uninfected controls. Analysis of serologic immune factors in the three strains revealed increased IgM and IgG3, and a general absence of inflammatory markers at two weeks post infection. Our data suggests that TLR4 function is not sufficient to cause susceptibility to leptospirosis. We conclude that C3H/HeN and C57BL/6 are appropriate mouse models of sublethal leptospirosis.