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| Status |
Public on Apr 22, 2019 |
| Title |
IL-21/type I interferon interplay regulates neutrophil-dependent innate immune responses to Staphylococcus aureus |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 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.
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| Overall design |
RNA-Seq analysis using total RNA either from total lung tissues isolated from mouse or from peripheral blood purified from normal donors or AD-HIES patients.
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| Contributor(s) |
Spolski R, West EE, Li P, Veenbergen S, Yung S, Kazemian M, Oh J, Yu Z, Freeman AF, Holland SM, Murphy PM, Leonard WJ |
| Citation(s) |
30969166 |
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| Submission date |
Mar 31, 2019 |
| Last update date |
Oct 09, 2019 |
| Contact name |
Peng Li |
| E-mail(s) |
peng.li@nih.gov
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| Organization name |
NIH
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| Department |
NHLBI
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| Lab |
LMI
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| Street address |
9000 Rockville Pike
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (3) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (28)
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| Relations |
| BioProject |
PRJNA530063 |
| SRA |
SRP189956 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE129093_RAW.tar |
20.9 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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