Initiation of innate immune responses often relies on pathogen sensing by tissue-resident myeloid cells, typically macrophages and dendritic cells. However, how the innate immune system senses and mounts an efficient response to intravascular infections remains unclear. Here, we addressed this question in the context of Neisseria meningitidis intravascular infection. We found that dermal macrophages can respond to these bacteria by secreting chemokines that allow neutrophil recruitment to the lumen of infected vessels. Single cell sequencing, flow cytometry analysis, and intravital imaging revealed that this process relies on a population of Lyve1+ FolR2+ perivascular macrophages that continuously samples the blood and elicits a pro-inflammatory response in response to N. meningitidis uptake. These results shed light on the key role played by perivascular macrophages in the immune surveillance of the vascular compartment and further provide a causal sequence of events leading to the initiation of innate immune responses against intravascular infections.
In previous studies, we also demonstrated that endothelial surface expression of E-selectin is differentially upregulated depending on the vascular bed during infection. Infections affecting capillaries and arterioles did not induce any specific E-selectin signal. In contrast, infected venules exhibited a progressive accumulation of E-selectin throughout the course of infection. Moreover, blocking E-selectin markedly impaired neutrophil recruitment in venules, despite ongoing robust vascular colonization.
To date, little is known about the status of endothelial cells during N. meningitidis infection, and further investigation is needed to better understand the communication between perivascular macrophages, neutrophils and endothelial cells.
