Fig. 5. Proposed model for regulation of virulence by VapBC22.

The imbalance in the relative levels of both VapC22 and VapB22 results in reduced expression of various virulence proteins. The virulence-associated proteins such as ESX-I, ESX-V, KasA, KasB, and AcpM modulate host immune response to enhance replication of intracellular M. tuberculosis. In agreement, the transcripts involved in innate immune responses as evident by induction of apoptosis, recruitment of M2 macrophages, neutrophils, and dendritic cells were enhanced in mice infected with ΔvapC22 strain. We propose that the repression of virulence-associated proteins in ΔvapC22 and VapB22 overexpression strain is associated with their faster clearance by the innate immune response resulting in reduced immunopathology.