In:
eLife, eLife Sciences Publications, Ltd, Vol. 8 ( 2019-04-16)
Abstract:
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 IFNβ 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.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.45501.001
DOI:
10.7554/eLife.45501.002
DOI:
10.7554/eLife.45501.003
DOI:
10.7554/eLife.45501.004
DOI:
10.7554/eLife.45501.005
DOI:
10.7554/eLife.45501.006
DOI:
10.7554/eLife.45501.007
DOI:
10.7554/eLife.45501.008
DOI:
10.7554/eLife.45501.009
DOI:
10.7554/eLife.45501.010
DOI:
10.7554/eLife.45501.011
DOI:
10.7554/eLife.45501.012
DOI:
10.7554/eLife.45501.013
DOI:
10.7554/eLife.45501.014
DOI:
10.7554/eLife.45501.015
DOI:
10.7554/eLife.45501.016
DOI:
10.7554/eLife.45501.017
DOI:
10.7554/eLife.45501.018
DOI:
10.7554/eLife.45501.019
DOI:
10.7554/eLife.45501.020
DOI:
10.7554/eLife.45501.021
DOI:
10.7554/eLife.45501.025
DOI:
10.7554/eLife.45501.026
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2019
detail.hit.zdb_id:
2687154-3