PMID- 18996346 OWN - NLM STAT- MEDLINE DCOM- 20081126 LR - 20200930 IS - 1934-6069 (Electronic) IS - 1931-3128 (Print) IS - 1931-3128 (Linking) VI - 4 IP - 5 DP - 2008 Nov 13 TI - Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens. PG - 458-69 LID - 10.1016/j.chom.2008.10.003 [doi] AB - The physiologic importance of autophagy proteins for control of mammalian bacterial and parasitic infection in vivo is unknown. Using mice with granulocyte- and macrophage-specific deletion of the essential autophagy protein Atg5, we show that Atg5 is required for in vivo resistance to the intracellular pathogens Listeria monocytogenes and Toxoplasma gondii. In primary macrophages, Atg5 was required for interferongamma (IFN-gamma)/LPS-induced damage to the T. gondii parasitophorous vacuole membrane and parasite clearance. While we did not detect classical hallmarks of autophagy, such as autophagosomes enveloping T. gondii, Atg5 was required for recruitment of IFN-gamma-inducible p47 GTPase IIGP1 (Irga6) to the vacuole membrane, an event that mediates IFN-gamma-mediated clearance of T. gondii. This work shows that Atg5 expression in phagocytic cells is essential for cellular immunity to intracellular pathogens in vivo, and that an autophagy protein can participate in immunity and intracellular killing of pathogens via autophagosome-independent processes such as GTPase trafficking. FAU - Zhao, Zijiang AU - Zhao Z AD - Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. FAU - Fux, Blima AU - Fux B FAU - Goodwin, Megan AU - Goodwin M FAU - Dunay, Ildiko R AU - Dunay IR FAU - Strong, David AU - Strong D FAU - Miller, Brian C AU - Miller BC FAU - Cadwell, Ken AU - Cadwell K FAU - Delgado, Monica A AU - Delgado MA FAU - Ponpuak, Marisa AU - Ponpuak M FAU - Green, Karen G AU - Green KG FAU - Schmidt, Robert E AU - Schmidt RE FAU - Mizushima, Noboru AU - Mizushima N FAU - Deretic, Vojo AU - Deretic V FAU - Sibley, L David AU - Sibley LD FAU - Virgin, Herbert W AU - Virgin HW LA - eng GR - R01 AI036629/AI/NIAID NIH HHS/United States GR - R01 AI042999/AI/NIAID NIH HHS/United States GR - AI071299/AI/NIAID NIH HHS/United States GR - U54 AI057160-010005/AI/NIAID NIH HHS/United States GR - R01 AI069345/AI/NIAID NIH HHS/United States GR - R37 AI042999/AI/NIAID NIH HHS/United States GR - AI036629/AI/NIAID NIH HHS/United States GR - U54 AI057160/AI/NIAID NIH HHS/United States GR - R21 AI071299/AI/NIAID NIH HHS/United States GR - R21 AI071299-02/AI/NIAID NIH HHS/United States GR - AI069345/AI/NIAID NIH HHS/United States GR - R01 AI036629-15/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell Host Microbe JT - Cell host & microbe JID - 101302316 RN - 0 (Atg5 protein, mouse) RN - 0 (Autophagy-Related Protein 5) RN - 0 (Microtubule-Associated Proteins) RN - 82115-62-6 (Interferon-gamma) SB - IM CIN - Cell Host Microbe. 2008 Nov 13;4(5):413-4. PMID: 18996340 MH - Animals MH - *Autophagy MH - Autophagy-Related Protein 5 MH - Cells, Cultured MH - *Host-Pathogen Interactions MH - Humans MH - Immunity, Cellular MH - Interferon-gamma/immunology MH - Listeria monocytogenes/*physiology MH - Listeriosis/*immunology/microbiology MH - Lysosomes/immunology/parasitology MH - Macrophages/*immunology/parasitology MH - Mice MH - Mice, Inbred CBA MH - Mice, Knockout MH - Microtubule-Associated Proteins/genetics/*immunology MH - Signal Transduction MH - Toxoplasma/*physiology MH - Toxoplasmosis/*immunology/parasitology PMC - PMC2682425 MID - NIHMS79827 EDAT- 2008/11/11 09:00 MHDA- 2008/12/17 09:00 PMCR- 2008/11/12 CRDT- 2008/11/11 09:00 PHST- 2008/06/01 00:00 [received] PHST- 2008/08/29 00:00 [revised] PHST- 2008/10/07 00:00 [accepted] PHST- 2008/11/11 09:00 [pubmed] PHST- 2008/12/17 09:00 [medline] PHST- 2008/11/11 09:00 [entrez] PHST- 2008/11/12 00:00 [pmc-release] AID - S1931-3128(08)00329-6 [pii] AID - 10.1016/j.chom.2008.10.003 [doi] PST - ppublish SO - Cell Host Microbe. 2008 Nov 13;4(5):458-69. doi: 10.1016/j.chom.2008.10.003.