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Macrophages disseminate pathogen associated molecular patterns through the direct extracellular release of the soluble content of their phagolysosomes

Catherine J. Greene, Jenny A. Nguyen, Samuel M. Cheung, Corey R. Arnold, Dale R. Balce, Ya Ting Wang, Adrian Soderholm, Neil McKenna, Devin Aggarwal, Rhiannon I. Campden, Benjamin W. Ewanchuk, Herbert W. Virgin and Robin M. Yates ()
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Catherine J. Greene: University of Calgary
Jenny A. Nguyen: University of Calgary
Samuel M. Cheung: University of Calgary
Corey R. Arnold: University of Calgary
Dale R. Balce: University of Calgary
Ya Ting Wang: Washington University School of Medicine
Adrian Soderholm: University of Calgary
Neil McKenna: University of Calgary
Devin Aggarwal: University of Calgary
Rhiannon I. Campden: University of Calgary
Benjamin W. Ewanchuk: University of Calgary
Herbert W. Virgin: Washington University School of Medicine
Robin M. Yates: University of Calgary

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Recognition of pathogen-or-damage-associated molecular patterns is critical to inflammation. However, most pathogen-or-damage-associated molecular patterns exist within intact microbes/cells and are typically part of non-diffusible, stable macromolecules that are not optimally immunostimulatory or available for immune detection. Partial digestion of microbes/cells following phagocytosis potentially generates new diffusible pathogen-or-damage-associated molecular patterns, however, our current understanding of phagosomal biology would have these molecules sequestered and destroyed within phagolysosomes. Here, we show the controlled release of partially-digested, soluble material from phagolysosomes of macrophages through transient, iterative fusion-fission events between mature phagolysosomes and the plasma membrane, a process we term eructophagy. Eructophagy is most active in proinflammatory macrophages and further induced by toll like receptor engagement. Eructophagy is mediated by genes encoding proteins required for autophagy and can activate vicinal cells by release of phagolysosomally-processed, partially-digested pathogen associated molecular patterns. We propose that eructophagy allows macrophages to amplify local inflammation through the processing and dissemination of pathogen-or-damage-associated molecular patterns.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30654-4

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DOI: 10.1038/s41467-022-30654-4

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