Abstract
Neutrophils play a key role in innate immunity. As the dominant circulating phagocyte, they are rapidly recruited from the bloodstream to sites of infection or injury to internalize and destroy microbes. More recently, neutrophils have been identified in uninfected organs, challenging the classical view of their function. Here we show that neutrophils were present in lymph nodes (LNs) in homeostasis. Using flow cytometry and confocal imaging, we identified neutrophils within LNs in naive, unchallenged mice, including LNs draining the skin, lungs, and gastrointestinal tract. Neutrophils were enriched within specific anatomical regions, in the interfollicular zone, a site of T cell activation. Intravital two-photon microscopy demonstrated that LN neutrophils were motile, trafficked into LNs from both blood and tissues via high endothelial venules and afferent lymphatics, respectively, and formed interactions with dendritic cells in LNs. Murine and human LN neutrophils had a distinct phenotype compared with circulating neutrophils, with higher major histocompatibility complex II (MHCII) expression, suggesting a potential role in CD4 T cell activation. Upon ex vivo stimulation with IgG immune complex (IC), neutrophils up-regulated expression of MHCII and costimulatory molecules and increased T cell activation. In vivo, neutrophils were capable of delivering circulating IC to LNs, suggesting a broader functional remit. Overall, our data challenge the perception that neutrophil patrol is limited to the circulation in homeostasis, adding LNs to their routine surveillance territory.
Highlights
Neutrophils play a key role in innate immunity
Our study demonstrates that neutrophils are present in unstimulated lymph nodes (LNs) under homeostatic conditions, in areas that enable them to interact with T cells, dendritic cells (DCs), and subcapsular sinus (SCS) macrophages
Circulating neutrophils traffic into LNs via high endothelial venules (HEVs) and lymphatic vessels, the former process involving peripheral lymph node addressin (PNAd), and neutrophils interact with DCs in LNs at baseline
Summary
Neutrophils play a key role in innate immunity. As the dominant circulating phagocyte, they are rapidly recruited from the bloodstream to sites of infection or injury to internalize and destroy microbes. Upon ex vivo stimulation with IgG immune complex (IC), neutrophils up-regulated expression of MHCII and costimulatory molecules and increased T cell activation. Neutrophils were capable of delivering circulating IC to LNs, suggesting a broader functional remit. Our data challenge the perception that neutrophil patrol is limited to the circulation in homeostasis, adding LNs to their routine surveillance territory. Highlighted neutrophils in uninflamed nonlymphoid organs including lung and intestine, suggesting they may contribute to tissue homeostasis [22]; whether this occurs in LNs is unclear. We address the question of whether neutrophils traffic tonically into LNs under homeostatic conditions, expanding the anatomical territories they routinely patrol, with the potential to bolster basal cellular innate defense in LNs and influence adaptive immunity by bringing blood-sampled antigen for presentation to CD4 T cells
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