NOD2 has been implicated in mycobacterial immunity through chemical, immunologic and epidemiologic evidence: 1) mycobacteria contain a distinct NOD2 agonist in that they possess N-glycolylated muropeptides while other bacteria have N-acetylated muropeptides (11, 12); 2) N-glycolylation of the muropeptide was shown to be a more potent activator of innate immune cells (13, 14) and Nod2-/- mice have decreased immune responses to mycobacteria (15, 16); 3) polymorphisms in NOD2 have been associated with several mycobacterial diseases including tuberculosis, leprosy and Buruli ulcer (17–20). Here, NOD2 is linked to leprosy.