Indispensable role of protein kinase D1 in inflammatory responses and host defense in Group B streptococci infection

• Published in: The Journal of immunology (1950) 2018-05, Vol.200 (1_Supplement), p.50-50.16
• Main Authors: Yoon, Taewon, Halder, Priyanka, Yi, Ae-Kyung
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.200.Supp.50.16

Group B streptococcus (GBS) causes life-threatening diseases in neonates and immune compromised individuals. We previously found that GBS induce activation of protein kinase D1 (PKD1) in mouse and human. This PKD1 activation by GBS is dependent on the TLR signaling adaptor MyD88 and its downstream IRAK4 and IRAK1. GBS-mediated proinflammatory cytokine production is substantially suppressed by pretreatment with a PKC/PKD inhibitor Gö6976. However, it is currently unknown whether PKD1 plays a regulatory role in GBS-mediated proinflammatory responses and host defense. In the present study, to further understand contribution of PKD1 in inflammatory responses and host defense in GBS infection, tamoxifen-inducible PKD1-deficient mice were generated. We found that GBS-mediated activation of MAPKs and NF-kB and expression of cytokines/chemokines are significantly inhibited in PKD1-deficient mice. Furthermore, increased susceptibility to GBS infection was observed in PKD1-deficient mice. However, PKD1-deficient mice sensitized with D-galactosamine were more resistant to the shock-mediated death caused by antibiotic-killed GBS compared to wild-type. Our findings imply that PKD1 is one of the critical factors that plays a regulatory role in GBS-induced proinflammatory reactions and is indispensable for host defense against GBS infection and that inhibition of PKD1 activation together with antibiotic treatment in GBS-infected neonates might be an effective way to control GBS diseases.