In conclusion, our data shows that C3H/HeN and C57BL/6 mice, both TLR4 competent strains, can be used to recapitulate sublethal leptospirosis as they produce unambiguous differences in clinical and molecular measurements of disease progression, Leptospira dissemination to tissues, colonization of kidney by live spirochetes and shedding in urine. Here, TLR4 is linked to leptospirosis.