Figure 8. Autophagy prevents tissue deterioration by antimicrobial defenses.

(a) Distribution of Listeria inside and outside of infectious foci. Percentage of total bacteria. n = 3, five images per animal. (b) Liver cfu values in Listeria-infected Becn1^+/+ and Becn1^+/− mice (d3). n = 3. (c) rRNA-positive and rRNA-negative bacteria in the livers of Listeria-infected mice of (d3). n = 3, ten images per animal. (d) Macrophage distribution inside and outside of infectious foci (d3). Left: Representative confocal microscopy images. Red, macrophages; blue, nuclei; empty arrowheads, extrafocal macrophages; full arrowheads, macrophages at margins of foci; stars, intrafocal macrophages. Scale bar, 50 μm. Data are representative of experiments on three different mice. Right: Quantitative analysis of macrophage distribution in infectious foci of Becn1^+/+ and Becn1^+/− mice. n = 3, ten images per animal. (e) Ly6C^high and Ly6C^low macrophages at margin and in core of infectious foci of Listeria-infected mice (d3). n = 3, 1 images per animal. (f) Tissue cytokine levels in Listeria-infected Becn1^+/+ and Becn1^+/− mice. n = 3 (IL-6, Becn1^+/−), n = 4 (Becn1^+/−), n = 6 (WT). (g) Representative western blot (from two different experiments) of TNF formation in LPS- or IFNγ-stimulated SR-BI_wt without or with reduced Atg7 expression. (h) Model of a bona fide immune pathway selectively controlling immunopathology. SR-BI detects products of antimicrobial defenses such as apoptotic immune cells and dead bacteria as well as (live) bacteria. As a response, SR-BI generates lipid domains which trigger internalization of apoptotic cells and bacteria and activate autophagic responses. In vivo, SR-BI- and beclin-1-dependent autophagy restricts neutrophil (N) infiltration, degrades host cell and bacterial corpses and prevents accumulation of Ly6C^high macrophages (Mϕ) in organs such as the liver. These mechanisms prevent hepatocyte (H) necrosis and suppress growth of infectious foci. Survival and intrafocal containment of bacteria are unchanged. Thereby, autophagy acts as effector of a surveillance pathway that restricts specifically organ damage by antimicrobial immunity. *P < 0.05, ***P < 0.001. One-way ANOVA with Bonferroni post-test correction (a), Kruskal-Wallis One Way Analysis of Variants on Ranks (c), t-test (d–f) and Mann-Whitney Rank Sum Test (f (TNF)).