| First Author | Spolski R | Year | 2019 |
| Journal | Elife | Volume | 8 |
| PubMed ID | 30969166 | Mgi Jnum | J:275111 |
| Mgi Id | MGI:6304127 | Doi | 10.7554/eLife.45501 |
| Citation | Spolski R, et al. (2019) IL-21/type I interferon interplay regulates neutrophil-dependent innate immune responses to Staphylococcus aureus. Elife 8:e45501 |
| abstractText | Methicillin-resistant Staphylococcus aureus (MRSA) is a major hospital- and community-acquired 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 intra-tracheally 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 anti-IFNAR1 treatment diminished MRSA clearance in these animals. Moreover, we found that IFNbeta 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. |
