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.
|Date of Award||Mar 2015|