Abstract
Autophagy, an evolutionally conserved homeostatic process for catabolizing cytoplasmic components, has been linked to the elimination of intracellular pathogens during mammalian innate immune responses. However, the mechanisms underlying cytoplasmic infection-induced autophagy and the function of autophagy in host survival after infection with intracellular pathogens remain unknown. Here we report that in drosophila, recognition of diaminopimelic acid–type peptidoglycan by the pattern-recognition receptor PGRP-LE was crucial for the induction of autophagy and that autophagy prevented the intracellular growth of Listeria monocytogenes and promoted host survival after this infection. Autophagy induction occurred independently of the Toll and IMD innate signaling pathways. Our findings define a pathway leading from the intracellular pattern-recognition receptors to the induction of autophagy to host defense.
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Acknowledgements
We thank D.A. Portnoy (University of California, Berkeley) and D.E. Higgins (Harvard Medical School) for L. monocytogenes strains; L.W. Cheng (University of California, Berkeley) for the S2 cell L. monocytogenes infection protocol; T.P. Neufeld (University of Minnesota) for Atg1Δ3D, Atg5IR, Atg1 and GFP-LC3; D. Hultmark (Umeå University) for RelishE20; K. Anderson (Cornell University) for PGRP-LC7454; A. Goto (Tohoku University) for hml-Gal4; the Bloomington Stock Center, Drosophila Genetic Resource Center at the Kyoto Institute of Technology and the Genetic Strain Research Center of National Institute of Genetics for fly stocks; and S. Iwanaga, M. Mitsuyama, A. Yamamoto and S. Natori for discussions. Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Japan Society for the Promotion of Science; the Program for the Promotion of Basic Research Activities for Innovative Biosciences; the National Institutes of Health (AI60025 and AI074958 to N.S.; AI074958); and the Naito Foundation.
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Yano, T., Mita, S., Ohmori, H. et al. Autophagic control of listeria through intracellular innate immune recognition in drosophila. Nat Immunol 9, 908–916 (2008). https://doi.org/10.1038/ni.1634
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DOI: https://doi.org/10.1038/ni.1634
