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Angiogenins: a new class of microbicidal proteins involved in innate immunity


Although angiogenins have been implicated in tumor-associated angiogenesis, their normal physiologic function remains unclear. We show that a previously uncharacterized angiogenin, Ang4, is produced by mouse Paneth cells, is secreted into the gut lumen and has bactericidal activity against intestinal microbes. Ang4 expression is induced by Bacteroides thetaiotaomicron, a predominant member of the gut microflora, revealing a mechanism whereby intestinal commensal bacteria influence gut microbial ecology and shape innate immunity. Furthermore, mouse Ang1 and human angiogenin, circulating proteins induced during inflammation, exhibit microbicidal activity against systemic bacterial and fungal pathogens, suggesting that they contribute to systemic responses to infection. These results establish angiogenins as a family of endogenous antimicrobial proteins.

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Figure 1: Tissue-specific patterns of expression of mouse angiogenin family members.
Figure 2: Ang4 localizes to Paneth cell secretory granules and is secreted in response to LPS.
Figure 3: Mouse and human angiogenins exhibit species-selective microbicidal activity.
Figure 4: Ang4 expression is induced by normal intestinal bacteria.

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We thank J. Dant for electron microscopy; S. Wagoner, C. Chen, D. O'Donnell and M. Karlsson for technical assistance; P. Cossart for providing Listeria strains; and M. Dunne for helpful suggestions. This work was supported by the NIH (DK30292 to J.I.G., DK02954 to T.S.S., and P30 DK52574 to L.V.H.), AstraZeneca (J.I.G.) and the Burroughs-Wellcome Fund (Career Award to L.V.H.).

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Correspondence to Jeffrey I. Gordon.

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Hooper, L., Stappenbeck, T., Hong, C. et al. Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat Immunol 4, 269–273 (2003).

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