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Distinct surveillance pathway for immunopathology during acute infection via autophagy and SR-BI
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Distinct surveillance pathway for immunopathology during acute infection via autophagy and SR-BI
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Distinct surveillance pathway for immunopathology during acute infection via autophagy and SR-BI
Distinct surveillance pathway for immunopathology during acute infection via autophagy and SR-BI
Journal Article

Distinct surveillance pathway for immunopathology during acute infection via autophagy and SR-BI

2016
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Overview
The mechanisms protecting from immunopathology during acute bacterial infections are incompletely known. We found that in response to apoptotic immune cells and live or dead Listeria monocytogenes scavenger receptor BI (SR-BI), an anti-atherogenic lipid exchange mediator, activated internalization mechanisms with characteristics of macropinocytosis and, assisted by Golgi fragmentation, initiated autophagic responses. This was supported by scavenger receptor-induced local increases in membrane cholesterol concentrations which generated lipid domains particularly in cell extensions and the Golgi. SR-BI was a key driver of beclin-1-dependent autophagy during acute bacterial infection of the liver and spleen. Autophagy regulated tissue infiltration of neutrophils, suppressed accumulation of Ly6C + (inflammatory) macrophages and prevented hepatocyte necrosis in the core of infectious foci. Perifocal levels of Ly6C + macrophages and Ly6C − macrophages were unaffected, indicating predominant regulation of the focus core. SR-BI-triggered autophagy promoted co-elimination of apoptotic immune cells and dead bacteria but barely influenced bacterial sequestration and survival or inflammasome activation, thus exclusively counteracting damage inflicted by immune responses. Hence, SR-BI- and autophagy promote a surveillance pathway that partially responds to products of antimicrobial defenses and selectively prevents immunity-induced damage during acute infection. Our findings suggest that control of infection-associated immunopathology can be based on a unified defense operation.