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However, the mechanisms involved in proinflammatory responses against GBS, as well as the contribution of signaling modulators involved in host immune defense, have not been fully elucidated. In the present study, we investigated the role of protein kinase D (PKD)1 in the proinflammatory responses to GBS. We found that both live and antibiotic-killed GBS induce activation of PKD1 through a pathway that is dependent on the TLR signaling adaptor MyD88 and its downstream kinase IL-1R\u2013associated kinase 1, but independent of TNFR-associated factor 6. Our studies using pharmacological PKD inhibitors and PKD1-knockdown macrophages revealed that PKD1 is indispensable for GBS-mediated activation of MAPKs and NF-\u03baB and subsequent expression of proinflammatory mediators. Furthermore, systemic administration of a PKD inhibitor protects d-galactosamine\u2013sensitized mice from shock-mediated death caused by antibiotic-killed GBS. These findings imply that PKD1 plays a critical regulatory role in GBS-induced proinflammatory reactions and sepsis, and inhibition of PKD1 activation together with antibiotic treatment in GBS-infected neonates could be an effective way to control GBS diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1601089","type":"journal-article","created":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T00:30:25Z","timestamp":1493685025000},"page":"4448-4457","source":"Crossref","is-referenced-by-count":19,"title":["Group B Streptococci Induce Proinflammatory Responses via a Protein Kinase D1\u2013Dependent Pathway"],"prefix":"10.1093","volume":"198","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5951-8686","authenticated-orcid":false,"given":"Kirtikumar","family":"Upadhyay","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The University of Tennessee Health Science Center , Memphis, TN 38163"},{"name":"Department of Obstetrics and Gynecology, The University of Tennessee Health Science Center , Memphis, TN 38163"},{"name":"Children\u2019s Foundation Research Institute, Le Bonheur Children\u2019s Hospital , Memphis, TN 38103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4080-4447","authenticated-orcid":false,"given":"Jeoung-Eun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Tennessee Health Science Center , Memphis, TN 38163"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Won","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center , Memphis, TN 38163"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Halder","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center , Memphis, TN 38163"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3215-2685","authenticated-orcid":false,"given":"Young-In","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Tennessee Health Science Center , Memphis, TN 38163"},{"name":"Children\u2019s Foundation Research Institute, Le Bonheur Children\u2019s Hospital , Memphis, TN 38103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5760-3852","authenticated-orcid":false,"given":"Victoria","family":"Metcalfe","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center , Memphis, TN 38163"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-9970","authenticated-orcid":false,"given":"Ajay J","family":"Talati","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Tennessee Health Science Center , Memphis, TN 38163"},{"name":"Department of Obstetrics and Gynecology, The University of Tennessee Health Science Center , Memphis, TN 38163"},{"name":"Children\u2019s Foundation Research Institute, Le Bonheur Children\u2019s Hospital , Memphis, TN 38103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4450-0715","authenticated-orcid":false,"given":"B Keith","family":"English","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University , Lansing, MI 48912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ae-Kyung","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center , Memphis, TN 38163"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,6,1]]},"reference":[{"key":"2025030615162184900_r1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1086\/422321","article-title":"Prevalence of group B Streptococcus colonization and potential for transmission by casual contact in healthy young men and women","volume":"39","author":"Manning","year":"2004","journal-title":"Clin. 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