TLR4-MyD88 activation by the leptospiral LPS therefore remains the best candidate to explain the species-specificity of the immune response to Leptospira. However, a recent study demonstrated that transgenic mice expressing human TLR4/MD2 are not more susceptible to leptospirosis than WT mice (Nair et al., 2021). This evidence concerns the gene LY96 and leptospirosis.