Recent advances on the crosstalk between neutrophils and B or T lymphocytes

Abstract

An increasing body of literature supports a role for neutrophils as players in the orchestration of adaptive immunity. During acute and chronic inflammatory conditions, neutrophils rapidly migrate not only to sites of inflammation, but also to draining lymph nodes and spleen, where they engage bidirectional interactions with B-and T-lymphocyte subsets. Accordingly, a relevant role of neutrophils in modulating B-cell responses under homeostatic conditions has recently emerged. Moreover, specialized immunoregulatory properties towards B or T cells acquired by distinct neutrophil populations, originating under pathological conditions, have been consistently described. In this article, we summarize the most recent data from human studies and murine models on the ability of neutrophils to modulate adaptive immune responses under physiological and pathological conditions and the mechanisms behind these processes.

Human neutrophils activated via TLR8 promote Th17 polarization through IL-23

“…In fact, the Th17 differentiation obtained after 1 week of in vitro culture derives from many polarizing signals on naïve CD4 + T cells and depends on the balance of different cytokines in the culture medium. Moreover, the experiments performed in the presence of anti‐IL‐23p19‐neutralizing Ab clearly demonstrate that IL‐23 present in supernatants from R848‐ (and R848 + TNF‐α)‐treated neutrophils is mainly responsible for their Th17‐promoting effects, thus emphasizing previous findings on the crosstalk between neutrophils and Th17 cells . Accordingly, human neutrophils and Th17 cells have been previously shown to reciprocally chemoattract each other via the production of various chemokines, including CCL20 from neutrophils and CXCL8 from Th17 cells .…”

Transcriptional regulation of neutrophil differentiation and function during inflammation

“…Upon infiltration into inflammation sites, neutrophils respond to pro‐inflammatory stimuli and become fully activated, a state that features the secretion of a variety of cytokines and chemokines, and the expression of co‐stimulatory molecules and MHC molecules, thereby influencing the activation of other leukocyte types, including T/B cells and dendritic cells. Neutrophil‐mediated regulations of T/B cells and dendritic cells has been reviewed elsewhere . Furthermore, recognition of microbial products by specific surface receptors, such as pattern recognition receptors (PPRs) induces an intensively interacting network of downstream signaling and subsequent nuclear translocation of signal‐dependent TFs, such as NF‐κB, IRFs, and AP‐1, to induce the expression of genes that associate with neutrophil specific functions (Fig.…”

“…Neutrophilmediated regulations of T/B cells and dendritic cells has been reviewed elsewhere. 71,72 Furthermore, recognition of microbial products by specific surface receptors, such as pattern recognition receptors (PPRs) induces an intensively interacting network of downstream signaling and subsequent nuclear translocation of signal-dependent TFs, such as NF-B, IRFs, and AP-1, to induce the expression of genes that associate with neutrophil specific functions (Fig. 3).…”

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 interaction between neutrophils and monocytes is particularly relevant to antimicrobial activity and inflammatory diseases.…”

“…[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. Neutrophil granule mobilization alters monocyte adhesion, migration, and bacterial phagocytosis and killing.…”