Congratulations to our Platform 1 Co-Lead Dr. Paul Kubes on this recent publication!
Abstract
The adaptive immune function of lymph nodes is dependent on constant recirculation of lymphocytes. In this article, we identify neutrophils present in the lymph node at steady state, exhibiting the same capacity for recirculation. In germ-free mice, neutrophils still recirculate through lymph nodes, and in mice cohoused with wild microbiome mice, the level of neutrophils in lymph nodes increases significantly. We found that at steady state, neutrophils enter the lymph node entirely via L-selectin and actively exit via efferent lymphatics via an S1P dependent mechanism. The small population of neutrophils in the lymph node can act as reconnaissance cells to recruit additional neutrophils in the event of bacterial dissemination to the lymph node. Without these reconnaissance cells, there is a delay in neutrophil recruitment to the lymph node and a reduction in swarm formation following Staphylococcus aureus infection. This ability to recruit additional neutrophils by lymph node neutrophils is initiated by LTB4. This study establishes the capacity of neutrophils to recirculate, much like lymphocytes via L-selectin and high endothelial venules in lymph nodes and demonstrates how the presence of neutrophils at steady state fortifies the lymph node in case of an infection disseminating through lymphatics.
The innate immune response has not been shown to be dependent on cell recirculation through lymph nodes because it does not require Ag for activation. Interestingly, neutrophils also have high levels of L-selectin, which they shed upon activation (Walzog B. et al., 1994). A low-affinity L-selectin ligand has been postulated to support some L-selectin–dependent rolling in peripheral tissues (Shigeta A. et al., 2008); however, its role appears redundant for neutrophil recruitment as inhibition of endothelial P-selectin and E-selectin abolishes neutrophil recruitment into most tissues whereas inhibition of L-selectin alone is not very effective at inhibiting neutrophil recruitment (Patel K D. & McEver R P., 1997). This begs the question, what do neutrophils use L selectin for and why?
Publication:Neutrophils Recirculate Through Lymph Nodes to Survey Tissues for Pathogens. Bogoslowski A, Wijeyesinghe S, Lee WY, Chen CS, Alanani S, Jenne C, Steeber DA, Scheiermann C, Butcher EC, Masopust D, Kubes P. The Journal of Immunology. 23 March 2020.
