Granulocytes as modulators of dendritic cell function

Abstract

Effector T cell development is directly driven by APCs, in particular, by antigen-primed dendritic cells (DCs). Depending on the pathogenic stimulus and the microenvironment, DCs induce proliferation and polarization of naive CD4 T cells into different effector subsets, such as Th1, Th2, Th17, or regulatory T cells (T). During inflammation, DCs are found in close proximity to other innate immune cells, including all granulocyte subtypes, which potentially influence the immunomodulatory capacities of DCs. Neutrophils, eosinophils, and basophils are rapidly recruited into infected tissues where their main function is to eliminate invading pathogens. Mast cells are tissue-resident granulocytes that also contribute to host defense against pathogens but have, thus far, primarily been associated with their detrimental roles in allergic diseases. Although granulocytes have always been considered essential in innate immunity, their ability to influence the development of adaptive immunity has long been overlooked. This view is now changing, as multiple studies showed significant modulating effects of granulocytes on key players of adaptive immunity, including DCs and lymphocytes. Neutrophils, eosinophils, basophils, and mast cells regulate recruitment and activation of DCs through the release of mediators or via direct cell-cell contact, thereby influencing antigen-specific T cell responses. In this review, we will summarize the current knowledge on the impact of granulocytes on DC functioning and the subsequent putative consequences of this cross-talk on T cell proliferation and polarization. Together, this overview underscores the importance of granulocyte-DC communication to establish optimal immune responses.

Chemoirradiated neutrophils and T cells differentially affect immune functions of APCs

“…In the present study, we could show that ECP‐treated neutrophils do not contribute to T cell activation and that activation of T lymphocytes by other stimuli can be suppressed by ECP‐treated neutrophils, showing a potential mechanism of how they can further contribute to ECP's clinical efficacy. Neutrophils may have different immunomodulatory effects on DC function, which can be mediated via cell‐cell contact, soluble factors, neutrophil extracellular traps, and ectosomes . There have been controversial theories on the effects of neutrophils on DCs.…”

“…Neutrophils may have different immunomodulatory effects on DC function, which can be mediated via cell-cell contact, soluble factors, neutrophil extracellular traps, and ectosomes. 39 There have been controversial theories on the effects of neutrophils on DCs. On one hand, neutrophils can attract DCs by the release of chemotactic factors.…”

Therapeutic targeting of neutrophil exocytosis

“…The regulation of the innate and adaptive immune systems by neutrophils has been reviewed extensively . Neutrophil granule contents participate in many regulatory activities, including those involving T cells, dendritic cells, B cells, and monocytes .…”

“…The regulation of the innate and adaptive immune systems by neutrophils has been reviewed extensively. [70][71][72][73][74][75][76][77][78][79] Neutrophil granule contents participate in many regulatory activities, including those involving T cells, dendritic cells, B cells, and monocytes. 70,72,73,80 The interaction between neutrophils and monocytes is particularly relevant to antimicrobial activity and inflammatory diseases.…”

Monoclonal antibody‐mediated killing of tumour cells by neutrophils

“…71 In addition, it was hypothesized that neutrophils act as danger sensors by communicating the presence of infection to dendritic cells ( Figure 5B). 72,73 Moreover, several in vivo studies have demonstrated the ability of neutrophils to transport antigen to lymphoid organs, which indirectly or directly promoted antigen cross-presentation to T cells ( Figure 5C). 74,75 Furthermore, it was shown that neutrophils promote maturation and function of NK cells ( Figure 5D).…”