Efferocytosis of Pathogen-Infected Cells

Abstract

The prompt and efficient clearance of unwanted and abnormal cells by phagocytes is termed efferocytosis and is crucial for organism development, maintenance of tissue homeostasis, and regulation of the immune system. Dying cells are recognized by phagocytes through pathways initiated via “find me” signals, recognition via “eat me” signals and down-modulation of regulatory “don’t eat me” signals. Pathogen infection may trigger cell death that drives phagocytic clearance in an immunologically silent, or pro-inflammatory manner, depending on the mode of cell death. In many cases, efferocytosis is a mechanism for eliminating pathogens and pathogen-infected cells; however, some pathogens have subverted this process and use efferocytic mechanisms to avoid innate immune detection and assist phagocyte infection. In parallel, phagocytes can integrate signals received from infected dying cells to elicit the most appropriate effector response against the infecting pathogen. This review focuses on pathogen-induced cell death signals that drive infected cell recognition and uptake by phagocytes, and the outcomes for the infected target cell, the phagocyte, the pathogen and the host.

β-catenin Signaling Regulates Cell Fate Decisions at the Transition Zone of the Chondro-Osseous Junction During Fracture Healing

“…Hematopoietic engulfment of detached chondrocytes is reminiscent of efferocytosis, a mechanism used by phagocytic cells to remove cellular debris for the resolution of tissue damage and during normal tissue development. 37,38 Phagocytosis is mediated by both professional and non-professional phagocytic cells including macrophages, dendritic cells, tissue-infiltrating monocytes, neutrophils, and eosinophils as well as epithelial cells of mammary epithelium and astrocytes in the brain. [38][39][40] However, in the majority of cases, phagocytic clearance is primarily undertaken by macrophages.…”

“…37,38 Phagocytosis is mediated by both professional and non-professional phagocytic cells including macrophages, dendritic cells, tissue-infiltrating monocytes, neutrophils, and eosinophils as well as epithelial cells of mammary epithelium and astrocytes in the brain. [38][39][40] However, in the majority of cases, phagocytic clearance is primarily undertaken by macrophages. 37 This is likely the case in the context of hematopoietic engulfment of chondrocytes during fracture repair, since we show macrophages are present at the Transition Zone.…”

β-glucan dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment

“…To differentiate shuttling from other mechanisms of pathogen entry into macrophages (such as direct phagocytosis, efferocytosis [9], metaforosis/lateral transfer [15], and trogocytosis [16]) it was critical to observe both the cellular origin of shuttled conidium and the moment of transfer. The only possible way to do this was to perform high-resolution 4D confocal microscopy with both high spatial and temporal resolution.…”

Inhibition of inflammasome activation by a clinical strain of Klebsiella pneumoniae impairs efferocytosis and leads to bacterial dissemination

“…This pattern of cell death results in the formation of a plasma membrane pore that causes water influx and cell swelling, in addition to the release of cellular contents as LDH and proinflammatory cytokines 37 . Host cell death is a well-spread response mechanism induced by different pathogens during the infection course 38 . K. pneumoniae strains are able to survive and proliferate inside macrophages by avoiding phagosome fusion with lysosomes 39 ; in the present study, we investigate the impact of caspase-1/11-mediated cell death induced by clinical strains of K. pneumoniae on the restriction of bacterial growth.…”