Figure 2

Inhibition of phagolysosomal maturation by MAP. MAP sulpholipds inhibit the formation of the phagolysosome by hindering the merging of the phagosome with the lysosome. SapM dephosphorylates phosphotidylinositol phosphates, disrupting membrane-trafficking regulation. V-ATPase is involved in phagosome-lysosome fusion. It is bound by mycobacterium protein PtpA and excluded from the phagosome thus inhibiting fusion. Rab5 stimulates fusion of early endosomes. Through retention of Rab5, as well as inhibition of recruitment of early endosomal autoantigen 1 (EEA1) to mycobacterial phagosomes, MAP is able to avert the maturation of endosomes into functional mycobacteriocidal compartments. Normally TACO is released from the phagosome allowing the lysosome to fuse. This release is inhibited by MAP. Mycobacteria are known to influence MAPK-p38 through LAM activation of TLR2. This ultimately leads to the inhibition of EEA1. TLR2 also induces production of IL-10 inhibiting a number of other innate immune signaling pathways.