Neutrophil Activation and Cytokine Responses in Immunity

Neutrophils, the most abundant circulating leukocytes, serve as first responders in innate immunity through rapid extravasation, chemotaxis and effector functions such as phagocytosis, degranulation and formation of neutrophil extracellular traps. Their activation is orchestrated by a repertoire of pattern-recognition receptors, including toll-like receptors, which detect microbial and damage-associated molecular patterns to initiate intracellular signalling cascades. Activated neutrophils both produce and respond to a diverse array of cytokines and chemokines—such as interleukin-1, interleukin-6, tumour necrosis factor-alpha and chemokine (CXC motif) ligand 8—that function in autocrine and paracrine loops to modulate inflammation and recruit additional immune cells. Emerging evidence underscores the importance of chromatin remodelling and transcription factor networks in controlling cytokine gene expression within neutrophils. Dysregulation of these processes contributes to chronic inflammatory diseases, sepsis and autoimmunity, while precise modulation of neutrophil activation and cytokine production holds promise for novel therapeutic strategies worldwide.

Research from Nature Portfolio

Recent studies have demonstrated that treatment of bacterial pathogens with plant-derived trans-anethole markedly enhances neutrophil secretion of key pro-inflammatory cytokines, including interleukin-1β, interleukin-6 and tumour necrosis factor-alpha, in human whole-blood models. Foundational work has elucidated that chromatin at the interleukin-6 locus in resting neutrophils is maintained in a closed conformation but undergoes restructuring upon toll-like receptor 8 activation, a process potentiated by autocrine tumour necrosis factor-alpha to enable robust interleukin-6 production. Complementary research has revealed that type I interferon signalling amplifies toll-like receptor 8-driven interleukin-6 synthesis via increased endogenous tumour necrosis factor-alpha release and enhanced recruitment of key transcriptional co-activators, delineating an autocrine feedback loop that intensifies neutrophil cytokine output.

Neutrophil Activation and Cytokine Responses in Immunity publication trend

The graph below shows the total number of articles in neutrophil activation and cytokine responses in immunity across all publications each year (not limited to Nature Index journals).

Technical terms

Neutrophil: A type of abundant innate immune cell that responds rapidly to infection by migrating to sites of inflammation.

Cytokine: A small secreted protein that mediates intercellular communication during immune responses, including pro- and anti-inflammatory signals.

Chemokine: A subset of cytokines that directs the migration of immune cells through concentration gradients.

Toll-like receptor (TLR): A pattern-recognition receptor on immune cells that detects microbial components and triggers intracellular signalling pathways.

Chromatin remodelling: The dynamic modification of chromatin structure that regulates access of transcription factors to DNA.

Degranulation: The release of granule-contained antimicrobial and signalling molecules from neutrophils upon activation.

Autocrine signalling: A form of cell signalling in which a cell secretes a factor that binds to receptors on its own surface, modulating its own function.

References

1. Immunomodulatory effects of trans-anethole-treated Staphylococcus aureus Newman strain. Scientific Reports (2023).
2. Chromatin remodelling and autocrine TNFα are required for optimal interleukin-6 expression in activated human neutrophils. Nature Communications (2015).
3. IFNα enhances the production of IL-6 by human neutrophils activated via TLR8. Scientific Reports (2016).
4. Unveiling Differential Responses of Granulocytes to Distinct Immunostimulants with Implications in Autoimmune Uveitis. Biomedicines (2023).
5. Induction of OCT2 contributes to regulate the gene expression program in human neutrophils activated via TLR8. Cell Reports (2021).