Specific recognition of apoptotic cells reveals a ubiquitous and unconventional innate immunity

Cvetanovic M, Mitchell JE, Patel V, Avner BS, Su Y, van der Saag PT, Witte PL, Fiore S, Levine JS, Ucker DS
Source: J Biol Chem
Publication Date: (2006)
Issue: 281(29): 20055-67
Research Area:
Cancer Research/Cell Biology
Immunotherapy / Hematology
Cells used in publication:
Species: mouse
Tissue Origin: embryo
Nucleofectorâ„¢ I/II/2b
The purpose of physiological cell death is the non-inflammatory clearance of cells that have become inappropriate or non-functional. Consistent with this function, the recognition of apoptotic cells by professional phagocytes, including macrophages and dendritic cells, triggers a set of potent anti-inflammatory responses manifest on multiple levels. The immediate-early inhibition of pro-inflammatory cytokine gene transcription in the phagocyte is a proximate consequence of recognition of the apoptotic corpse, independent of subsequent engulfment and soluble factor involvement. Here, we show that recognition is linked to a characteristic signature of responses, including MAP kinase signaling events and the ablation of pro-inflammatory transcription and cytokine secretion. Specific recognition and response occurs without regard to the origin (species, tissue type, or suicidal stimulus) of the apoptotic cell, and does not involve Toll-like receptor signaling. These features mark this as an innate immunity fundamentally distinct from the discrimination of "self" versus "other" considered to be the hallmark of conventional immunity. This profound unconventional innate immune discrimination of effete from live cells is as ubiquitous as apoptotic cell death itself, manifest by professional and non-professional phagocytes and non-phagocytic cell types alike. Innate apoptotic immunity provides an intrinsic anti-inflammatory circuit that attenuates pro-inflammatory responses dynamically and may act systemically as a powerful physiological regulator of immunity.