IL-21/type I interferon interplay regulates neutrophil-dependent innate immune responses to Staphylococcus aureus
2019
textabstractMethicillin-resistant Staphylococcus aureus (MRSA) is a major hospital- and communityacquired pathogen, but the mechanisms underlying host-defense to MRSA remain poorly
understood. Here, we investigated the role of IL-21 in this process. When administered intratracheally into wild-type mice, IL-21 induced granzymes and augmented clearance of pulmonary
MRSA but not when neutrophils were depleted or a granzyme B inhibitor was added.
Correspondingly, IL-21 induced MRSA killing by human peripheral blood neutrophils.
Unexpectedly, however, basal MRSA clearance was also enhanced when IL-21 signaling was
blocked, both in Il21r KO mice and in wild-type mice injected with IL-21R-Fc fusion-protein. This
correlated with increased type I interferon and an IFN-related gene signature, and indeed antiIFNAR1 treatment diminished MRSA clearance in these animals. Moreover, we found that IFNb
induced granzyme B and promoted MRSA clearance in a granzyme B-dependent fashion. These
results reveal an interplay between IL-21 and type I IFN in the innate immune response to MRSA
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