Universität zu Köln

Gluschko, Alexander, Herb, Marc ORCID: 0000-0002-7533-0288, Wiegmann, Katja, Krut, Oleg, Neiss, Wolfram F., Utermoehlen, Olaf, Kroenke, Martin and Schramm, Michael (2018). The beta(2) Integrin Mac-1 Induces Protective LC3-Associated Phagocytosis of Listeria monocytogenes. Cell Host Microbe, 23 (3). S. 324 - 343. CAMBRIDGE: CELL PRESS. ISSN 1934-6069

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Abstract

The intracellular pathogen Listeria monocytogenes (L.m.) is targeted by the autophagic machinery, but the molecular mechanisms involved and consequences for anti-listerial immunity remain enigmatic. Here, we demonstrate that L.m. infection of macrophages in vivo exclusively evokes LC3-associated phagocytosis (LAP), but not canonical autophagy, and that targeting of L.m. by LAP is required for anti-listerial immunity. The pathway leading to LAP induction in response to L.m. infection emanates from the beta(2) integrin Mac-1 (CR3, integrin alpha(M)beta(2)), a receptor recognizing diverse microbial ligands. Interaction of L.m. with Mac-1 induces acid sphingomye-linase-mediated changes in membrane lipid composition that facilitate assembly and activation of the phagocyte NAPDH oxidase Nox2. Nox2-derived reactive oxygen species then trigger LC3 recruitment to L.m.-containing phagosomes by LAP. By promoting fusion of L.m.-containing phagosomes with lysosomes, LAP increases exposure of L.m. to bactericidal acid hydrolases, thereby enhancing anti-listerial activity of macrophages and immunity of mice.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gluschko, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Herb, Marc UNSPECIFIED orcid.org/0000-0002-7533-0288 UNSPECIFIED Wiegmann, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Krut, Oleg UNSPECIFIED UNSPECIFIED UNSPECIFIED Neiss, Wolfram F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Utermoehlen, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroenke, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schramm, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-192747
DOI:	10.1016/j.chom.2018.01.018
Journal or Publication Title:	Cell Host Microbe
Volume:	23
Number:	3
Page Range:	S. 324 - 343
Date:	2018
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1934-6069
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACID SPHINGOMYELINASE; INTRACELLULAR GROWTH; COMPLEMENT RECEPTOR; MOUSE MACROPHAGES; LC3 RECRUITMENT; AUTOPHAGY; MICE; IMMUNITY; INNATE; RECOGNITION Multiple languages Microbiology; Parasitology; Virology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19274