Immunoreceptors on neutrophils

Abstract

Neutrophils play a critical role in the host defense against infection, and they are able to perform a variety of effector mechanisms for this purpose. However, there are also a number of pathological conditions, including autoimmunity and cancer, in which the activities of neutrophils can be harmful to the host. Thus the activities of neutrophils need to be tightly controlled. As in the case of other immune cells, many of the neutrophil effector functions are regulated by a series of immunoreceptors on the plasma membrane. Here, we review what is currently known about the functions of the various individual immunoreceptors and their signaling in neutrophils. While these immunoreceptors allow for the recognition of a diverse range of extracellular ligands, such as cell surface structures (like proteins, glycans and lipids) and extracellular matrix components, they commonly signal via conserved ITAM or ITIM motifs and their associated downstream pathways that depend on the phosphorylation of tyrosine residues in proteins and/or inositol lipids. This allows for a balanced homeostatic regulation of neutrophil effector functions. Given the number of available immunoreceptors and their fundamental importance for neutrophil behavior, it is perhaps not surprising that pathogens have evolved means to evade immune responses through some of these pathways. Inversely, some of these receptors evolved to specifically recognize these pathogens. Finally, some interactions mediated by immunoreceptors in neutrophils have been identified as promising targets for therapeutic intervention.

Genetic variation of human neutrophil Fcγ receptors and SIRPα in antibody‐dependent cellular cytotoxicity towards cancer cells

“…Therefore, there is a pertinent need to improve the efficacy of cancer therapeutic antibodies. We and others have previously demonstrated that targeting the interaction between CD47 expressed on cancer cells and the inhibitory immunoreceptor SIRPα expressed on myeloid cells substantially potentiates the capacity of anti-cancer antibodies, including Trastuzumab and Rituximab [11][12][13], for recent reviews see [14][15][16]. Consistent with this notion the clinical response of either breast cancer patients treated with Trastuzumab or Non-Hodgkin lymphoma patients treated with Rituximab was better when CD47 expression levels in the tumor cells were lower [11,13].…”

Plasticity in Pro- and Anti-tumor Activity of Neutrophils: Shifting the Balance

“…Recent research has been focusing on further augmenting the anti-tumor responses of neutrophils, i.e., by trying to switch off the brakes. Neutrophils express a variety of inhibitory receptors on their cell surface ( 211 ) providing potential therapeutic targets for checkpoint-blockade therapy. One well-established example of successful checkpoint-blockade on neutrophils is CD47-signal regulatory protein alpha (SIRPα) disruption ( 212 ).…”

Granulocyte colony-stimulating factor as a checkpoint of the embryo invasive potential and endometrial receptivity

“…Вопреки примитивным представлениям о противоинфекционном иммунитете с участием нейтрофилов (Нф) данные клеточные элементы иммунной системы способны оказывать регуляторное действие на другие клетки, участвующие в регуляции иммунных процессов (рис. 1) [10]. Неспособность к прямому киллингу внутриклеточных патогенов компенсируется регуляторными свойствами Нф: киллинг происходит опосредованно через Тх 1-го типа [11].…”