Neutrophils in secondary lymphoid organs

Neutrophils are traditionally considered short-lived, circulating innate immune cells that are rapidly recruited to sites of inflammation in response to infectious and inflammatory stimuli. Neutrophils efficiently internalize, kill or entrap pathogens, but their effector molecules may cause collateral tissue damage. More recently, it has been appreciated that neutrophils can also influence adaptive immunity. Lymph nodes (LNs) are immune cell-rich secondary lymphoid organs that provide an ideal platform for cellular interaction and the integration of immunological information collected from local tissues. A variety of peripheral stimuli promote neutrophil migration to draining LNs via blood or lymphatics, utilizing differing molecular cues depending on the site of entry. Within LNs, neutrophils interact with other innate and adaptive cells. Crosstalk with subcapsular sinus macrophages contributes to the control of pathogen spread beyond the LN. Neutrophils can influence antigen presentation indirectly by interacting with DCs or directly by expressing major histocompatibility complex (MHC) and costimulatory molecules for antigen presentation. Interactions between neutrophils and adaptive lymphocytes can alter B-cell antibody responses. Studies have shown conflicting results on whether neutrophils exert stimulatory or inhibitory effects on other LN immune cells, with stimulus-specific and temporal differences in the outcome of these interactions. Furthermore, neutrophils have also been shown to traffick to LNs in homeostasis, with a potential role in immune surveillance, antigen capture and in shaping early adaptive responses in LNs. Understanding the mechanisms underpinning the effects of neutrophils on LN immune cells and adaptive immunity could facilitate the development of neutrophil-targeted therapies in inflammatory diseases.