Feeding a Fever

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Science  10 Sep 2010:
Vol. 329, Issue 5997, pp. 1261
DOI: 10.1126/science.329.5997.1261-b

Starvation or poor nutrition weakens the immune system and makes organisms more susceptible to disease. This reflects in part the need for adequate energy stores. But Mieulet et al. provide evidence that sufficient uptake of the amino acid arginine is required for mouse macrophages to respond to bacterial lipopolysaccharide, which binds to Toll-like receptors that initiate innate immune responses. Macrophages deprived of arginine appeared to have a deficit in the activation of mitogen-activated protein kinases (MAPKs) that mediate the immune response. In cultured cells deprived of arginine, the protein kinase TPL-2 (tumor-promoting locus 2, a MAPK kinase kinase) was associated to a greater extent with protein phosphatase 2A, leading to dephosphorylation and inactivation of TPL-2. In mice, deprivation of arginine also reduced MAPK activation and the consequent production of tumor necrosis factor–α. Arginine thus appears to have multiple important roles in the innate immune response: It serves as a substrate for the synthesis of nitric oxide as part of cellular response to bacterial infection, and it maintains a key signaling pathway that allows macrophages to fight infection effectively.

Sci. Signal. 3, ra61 (2010).

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