Genetic Diversity of Toll-Like Receptors and Immunity to M. leprae Infection

Figure 2

Arginine (R) is required as a substrate for inducible nitric oxide synthase (iNOS) in the production of nitric oxide. Nitric oxide contributes to microbial killing by combining with reactive oxygen intermediates in the phagolysosome to produce highly toxic peroxynitrite. Activation of surface TLR2 and TLR1 602I by mycobacterial products, including the 19 kDa lipoprotein, induces transcription of arginase-1 in a CEBPβ-dependent manner. Arginase-1 reduces substrate availability for iNOS by breaking down arginine, reducing the production of reactive oxygen species and favoring mycobacterial survival. TLR1 602S does not traffic to the cell surface (dashed lines) and therefore does not form a TLR1/2 signaling complex which would normally dampen the oxidative burst.