Journal
JOURNAL OF IMMUNOLOGY
Volume 181, Issue 3, Pages 2044-2055Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.3.2044
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Funding
- NIAID NIH HHS [AI053137, R01 AI053137-04, R01 AI053137] Funding Source: Medline
- NIAMS NIH HHS [AR47757, R03 AR047757-03] Funding Source: Medline
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Protein kinase D1 (PKD1) is expressed ubiquitously and regulates diverse cellular processes such as oxidative stress, gene expression, cell survival, and vesicle trafficking. However, the presence and function of PKD1 in monocytic cells are currently unknown. In this study, we provide evidence that PKD1 is involved in TLR9 signaling in macrophages. Class B-type CpG DNA (CpG-B DNA) induced activation of PKD1 via a pathway that is dependent on endosomal pH, TLR9, MyD88, and IL-1R-associated kinase I in macrophages. Upon CpG-B DNA stimulation, PKD1 interacted with the TLR9/MyD88/IL-1R-associated kinase/TNFR-associated factor 6 complex. Knockdown of PKD1 revealed that PKD1 is required for activation of NF-kappa B and MAPKs, and subsequent expression of cytokines in response to CpG-B DNA. Our findings identify PKD1 as a key signaling modulator in TLR9-mediated macrophage activation.
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