NOD2 and leprosy: Genetic variations of genes in the NOD2-mediated signaling pathway are associated with susceptibility to infection with M. leprae had been identified in leprosy patients.[27,28] NOD2 and RIPK2 interact to activate the NF-κB pathway, which affects the host's immune defense against infection.[29,30] Another possibility is that M. leprae damaged host immune system, reconstructed host immune microbial ecology to a new balance, even if M. leprae were removed,[12,31,32] which lead to the lower immune response to vaccination.