Immune complex-induced apoptosis and concurrent immune complex clearance are anti-inflammatory neutrophil functions

Utsa Karmakar (1) , Julia Chu (1) , Kruthika Sundaram (1) , Anne Laurence Astier (2, 1) , Hannah Garside (1) , Carsten Hansen (1) , Ian Dransfield (1) , Sonja Vermeren (1)

1 Edin. - University of Edinburgh
2 CPTP - Centre de Physiopathologie Toulouse Purpan

Abstract : Persistent neutrophilic inflammation drives host damage in autoimmune diseases that are characterized by abundant immune complexes. Insoluble immune complexes (iICs) potently activate pro-inflammatory neutrophil effector functions. We and others have shown that iICs also promote resolution of inflammation via stimulation of neutrophil apoptosis. We demonstrate here that iICs trigger FcγRIIa-dependent neutrophil macropinocytosis, leading to the rapid uptake, and subsequent degradation of iICs. We provide evidence that concurrent iIC-induced neutrophil apoptosis is distinct from phagocytosis-induced cell death. First, uptake of iICs occurs by FcγRII-stimulated macropinocytosis, rather than phagocytosis. Second, production of reactive oxygen species, but not iIC-internalization is a pre-requisite for iIC-induced neutrophil apoptosis. Our findings identify a previously unknown mechanism by which neutrophils can remove pro-inflammatory iICs from the circulation. Together iIC clearance and iIC-induced neutrophil apoptosis may act to prevent the potential escalation of neutrophilic inflammation in response to iICs.

Domaines: Immunologie; Sciences du Vivant [q-bio]

Utsa Karmakar, Julia Chu, Kruthika Sundaram, Anne Laurence Astier, Hannah Garside, et al.. Immune complex-induced apoptosis and concurrent immune complex clearance are anti-inflammatory neutrophil functions. Cell Death and Disease, 2021, 12, pp.296. ⟨10.1038/s41419-021-03528-8⟩. ⟨hal-03365812⟩