Innate apoptotic immunity: A potent immunosuppressive response repertoire elicited by specific apoptotic cell recognition

Abstract

Phagocytosis, of course, is essential for the clearance of dying cells, and for the degradation of dying cell constituents, including the processing of potential cellular [auto]antigens. Independent of engulfment, the specific recognition of dying cells by phagocytes and other cells elicits a profound repertoire of outcomes. In particular, apoptotic cells are potently suppressive of inflammation and other immunological responses. Immunosuppressive apoptotic effects are elicited in macrophages and dendritic cells, and they are triggered in non-professional phagocytes as well. Among these responses, the immediate-early suppression of specific gene transcription is most evident. The array of genes suppressed upon apoptotic recognition includes pro-inflammatory cytokines and angiogenic factors. The ability of apoptotic cells to elicit these responses depends upon their cell surface expression of specific determinants for recognition. A variety of molecules has been implicated in this process, although the identification of definitive recognition determinants remains incomplete. The suppressive effects exerted by apoptotic cells do not arise as a simple antagonism of stimulatory signals. Selective responsiveness to apoptotic cell recognition occurs independent of known immune receptors and signalling pathways. Remarkably, specific apoptotic recognition, in contrast to all other cases of immune discrimination, exhibits no self-bias. These observations suggest that innate apoptotic immunity represents an unconventional and ubiquitous immune responsiveness-in essence, a second dimension of immunity distinct from the classical self/other axis. The subversion by pathogens (including viruses) of this suppressive responsiveness underscores the physiological significance of innate apoptotic immunity. © 2009 Springer Netherlands.