Tuberculosis is endemic in the Gambian population, in which the magnitude of mycobacterial antigen-driven interferon-γ (IFN-γ) response in BCG vaccinated neonates has been linked to regions on the genome that encode the RIP2 kinase, the toll-like receptor 4 adapter protein MD-2 and the NF-κB subunit NF-κB2 by genome-wide linkage analysis. The receptor interacting protein (RIP2) is an essential kinase downstream of the nucleotide-binding oligomerization domain-containing protein 1 (NOD1) and NOD2, both intracellular pattern-recognition receptors for peptidoglycan moieties that induce activation of NF-κB. To establish the significance of RIP2 kinase during Mycobacterium tuberculosis infection, RIP2 was depleted in THP-1- derived macrophages using small interfering RNAs. In the absence of RIP2, THP- 1-derived macrophages secreted significantly reduced levels of the proinflammatory cytokine IL-1β upon infection with M. tuberculosis.