Innate immune cells generate the early host response to infection and tissue injury. Neutrophils are rapidly recruited from circulation to inflammatory tissues for pathogen killing. Type 2 innate lymphoid cells (ILC2s) mediate early responses to helminths and allergens via cytokine production. Innate immune cells interact with adaptive immune cells, for example via major histocompatibility complex class II (MHCII) expression for antigen presentation. Secondary lymphoid organs, including lymph nodes (LNs) and Peyer’s patches, are ideal sites for innate-adaptive cellular interactions.
Whilst neutrophils migrate to LNs following inflammation, whether this occurs in homeostasis is unclear. I demonstrated the presence of neutrophils under homeostatic conditions in LNs from unstimulated mice and human organ donors, trafficking into LNs via blood and lymphatic vessels. LN neutrophils were located in interfollicular areas, and expressed MHCII at baseline. Ex vivo, immune complex (IC) stimulation upregulated neutrophil expression of MHCII and co-stimulatory molecules, and increased antigen-specific CD4+ T cell activation. In vivo, neutrophils were capable of delivering circulating IC into LNs, and interacted with dendritic cells at baseline. Overall, these data suggest a novel role of neutrophils in homeostatic immune surveillance, routinely patrolling LNs and delivering systemic antigen to influence adaptive immunity.
To date little data exist on ILC2 behaviour in lymphoid tissues in vivo. Using two helminth inflammatory models, I demonstrated that ILC2s were the early source of interleukin-13. ILC2s were in T cell areas of LNs and Peyer’s patches, and increased in cell number, size and speed of movement following inflammatory challenge, suggesting a potential role in cytokine distribution. Within small bowel wall ILC2s interacted with T cells, suggesting a broader role in activating tissue T cells. Overall, these data provide novel insights into ILC2 behaviour in vivo.
Neutrophils and ILC2s are involved in chronic inflammatory diseases, but few neutrophil- or ILC2-targeted treatments exist. These data represent new knowledge on neutrophil and ILC2 behaviour within LNs, facilitating development of therapeutic approaches to these diseases.