Human neutrophilic cells express anti-inflammatory EBI3 in response to Neisseria meningitidis.

During bacterial infections of the central nervous system (CNS), the glia-neutrophil axis can drive a vicious cycle that results in lethal neuroinflammation. However, it is becoming apparent that glia can also be a significant source of immunosuppressive factors following bacterial challenge, presumably to mitigate inflammatory CNS damage. Similarly, neutrophils are known to express anti-inflammatory mediators following activation but their ability to produce them in response to clinically important neurotropic bacteria is poorly understood. In the present study, we have characterized the responses of a differentiated human neutrophil cell line to Neisseria meningitidis challenge by RNA Tag-Seq analysis and show marked enrichment in the expression of genes associated with Toll-like receptor-mediated NF-κB and AP-1 signaling, and inflammatory gene products. Interestingly, we also describe their upregulated expression of EBI3, a molecule that can exert immunosuppressive effects outside of its role as a component of IL-27 and IL-35. We have confirmed that these neutrophils produce and secrete EBI3 following N. meningitidis challenge, and we have begun to assess the functional ramifications of such production with the demonstration that EBI3 can significantly reduce the production of CXCL8 by infected primary human astrocytes. These results raise the possibility that neutrophils recruited to the CNS during N. meningitidis infection produce EBI3, thereby limiting inflammatory glial responses to this neurotropic bacterium.