Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation

Claudia Z. Han, Ignacio J. Juncadella, Jason M. Kinchen, Monica W. Buckley, Alexander L. Klibanov, Kelly Dryden, Suna Onengut-Gumuscu, Uta Erdbrügger, Stephen D. Turner, Yun M. Shim, Kenneth S. Tung, Kodi S. Ravichandran

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

Abstract

Professional phagocytes (such as macrophages) and non-professional phagocytes (such as epithelial cells) clear billions of apoptotic cells and particles on a daily basis. Although professional and non-professional macrophages reside in proximity in most tissues, whether they communicate with each other during cell clearance, and how this might affect inflammation, is not known. Here we show that macrophages, through the release of a soluble growth factor and microvesicles, alter the type of particles engulfed by non-professional phagocytes and influence their inflammatory response. During phagocytosis of apoptotic cells or in response to inflammation-associated cytokines, macrophages released insulin-like growth factor 1 (IGF-1). The binding of IGF-1 to its receptor on non-professional phagocytes redirected their phagocytosis, such that uptake of larger apoptotic cells was reduced whereas engulfment of microvesicles was increased. IGF-1 did not alter engulfment by macrophages. Macrophages also released microvesicles, whose uptake by epithelial cells was enhanced by IGF-1 and led to decreased inflammatory responses by epithelial cells. Consistent with these observations, deletion of IGF-1 receptor in airway epithelial cells led to exacerbated lung inflammation after allergen exposure. These genetic and functional studies reveal that IGF-1- and microvesicle-dependent communication between macrophages and epithelial cells can critically influence the magnitude of tissue inflammation in vivo.

Original languageEnglish
Pages (from-to)570-574
Number of pages5
JournalNature
Volume539
Issue number7630
DOIs
StatePublished - Nov 24 2016

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