Top shows two autophagy factors identified as Crohn’s disease (a form of inflammatory bowel disease) susceptibility loci. The IRGM gene has single nucleotide polymorphisms (SNP)and a 20 kb deletion in the promoter region associated with CD. ATG16L1 alleles encode either a protective ATG16L1*300T or a risk form of ATG16L1*300A (CCD, coiled coil domain; green boxes, WD repeats domain [absent in yeast Atg16]). Middle panel shows intestinal epithelium with different cell types along with the proposed functions of autophagy in the ileal epithelium. Side box shows that thymic selection of naive T cell repertoires depends on autophagy, and autophagic anomalies may contribute to inflammation at peripheral sites such as intestinal mucosa. Bottom box lists 3 different effects reported for Atg16L1 (mouse) or ATG16L1 (human epithelial cells) mutations. ATG16L1*300A has been tested in cell lines. Atg16L1^HM, hypomorphic Atg16L1 allele, and Atg16LΔCCD construct have been tested in vivo in transgenic mice.

(A) Electron micrograph comparing the appearance of an autophagosome (1) versus autolysosome (2) with conventional lysosomes (Ly).
(B) A composite of autophagic membrane formation (schematic) with actual autophagosome from an electron micrograph. Three stages can be discerned by ultrastructural morphology: initiation (crescent membrane decorated on both ssides with Atg protein-lipid [Atg8-PE; known as LC3-II] and protein-protein conjugates [Atg12-Atg5, complexed with Atg16]), elongation (growth of isolation membrane) ending in its closure to form an autophagosome, and maturation that involves the formation of degradative autolysosomes through fusion of autophagosomes with lysosomal organelles (electron-dense granular material represents ribosomal degradation intermediates). All micrographs in (A) and (B) are courtesy of Eeva-Lisa Eskalinen (reproduced with permission)
(C) Two signaling systems control induction of autophagy: left, hVps34-Beclin 1; right, Tor-Atg1. Various signals and systems transmitting them that lead to autophagy activation are shown in smaller boxes. Rapamycin induces autophagy by inhibiting Tor, and some immune signals that are transmitted via TLR adapters MyD88 and TRIF or DAPK downstream of IFNγ lead to activation of Beclin 1 (complexed with the phosphatidylinositol 3 kinase hVps34) by its dissociation from Bcl-2. Note that starvation, a classical inducer of autophagy, affects both Bcl-2-Beclin 1 complex (via JNK1) and Tor activity. Th2 cytokines and many growth factors in general inhibit autophagy via Tor (or in the case of immunologically induced autophagy, e.g., by IFNγ, via Stat-6 downstream of IL-4/IL-13).
(D)Immunological inputsand outputs of autophagy. Xenophagy,autophagic Macrophage activation, additional terms, factors, and relationships are described in the text.

See Table 1 and Table 2 for further details of specific host autophagy-pathogen interactions.