Research ArticleImmunology

Arginine Usage in Mycobacteria-Infected Macrophages Depends on Autocrine-Paracrine Cytokine Signaling

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Science Signaling  17 Aug 2010:
Vol. 3, Issue 135, pp. ra62
DOI: 10.1126/scisignal.2000955

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Spreading Suppression

The amino acid arginine, a critical component in the earliest responses of the immune system to infection, is the substrate for inducible nitric oxide synthase (iNOS), which generates the antimicrobial compound NO in macrophages. In infected macrophages, mycobacteria stimulate a pathway that depends on the Toll-like receptor adaptor protein MyD88 to increase the production of Arg1, an enzyme that breaks down arginine, removing the source of NO and thereby dampening the immune response (see the Perspective by Morris). Qualls et al. showed that MyD88 was required for the production of cytokines that acted in an autocrine manner to drive the expression of Arg1 in the infected cells. However, these cytokines also acted on uninfected macrophages, thus inhibiting their ability to produce NO in the absence of infection. The generation of such a suppressed situation in vivo would enable spread of the infection.