PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves
Fig 11
A model proposing a key role for the PGL I-induced CD206/PPARγ crosstalk in M. leprae neuropathogenesis.
The first step (signal 1) of the pathway activation initiates through PGL I recognition via laminin-2 [12] allowing bacterial internalization. Bacterial sensing by TLR6 also contributes to bacterial entry [22]. Additionally, the recognition of M. leprae ManLAM by baseline levels of CD206 allows some bacterial entry and weak activation of PPARγ, with subsequent CD206 upregulation. The higher expression of CD206 results in increasing bacterial sensing by this pathway, triggering a stronger second signal (signal 2), where internalized M. leprae promotes the amplification of CD206/ PPARγ crosstalk, inducing the accumulation of LDs and their recruitment to bacterium-containing phagosomes. The higher levels of LDs promote the production of PGE-2 and IL-10 [22], which favors the inhibition of SC´s antimicrobial mechanisms. CD206/ PPARγ crosstalk also induces IL-8 secretion that may be involved in demyelination and neuroinflammation. Narrow arrows indicate the initials steps involved in M. leprae-SC interaction. Wide arrows indicate the major steps involved in the amplification loop of the PPAR/CD206 crosstalk. DG = Dystroglycan, α2 LN = alpha 2 laminin, RXR = Retinoid X Receptor.