Protein kinase D mediates inflammatory responses of human placental macrophages to Group B Streptococcus

• Published in: American journal of reproductive immunology (1989) Vol. 81; no. 3; pp. e13075 - n/a
• Main Authors: Sutton, Jessica A., Rogers, Lisa M., Dixon, Beverly R.E.A., Kirk, Leslie, Doster, Ryan, Algood, Holly M., Gaddy, Jennifer A., Flaherty, Rebecca, Manning, Shannon D., Aronoff, David M.
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.03.2019
• Subjects: Cell activation; Cells, Cultured; Chorioamnionitis; cytokine; Cytokines - metabolism; Female; Fetuses; Gene expression; Group B Streptococcus; Humans; Immune response; infection; inflammasome; Inflammasomes; Inflammasomes - metabolism; Inflammation; Inflammation - immunology; Kinases; Macrophages; Macrophages - immunology; NF-kappa B - metabolism; NF-κB protein; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Phenotypes; Placenta; Placenta - immunology; placental macrophage; Pregnancy; Protein kinase; Protein Kinase C - immunology; Reproductive system; Signal Transduction; Streptococcal Infections - immunology; Streptococcus; Streptococcus agalactiae - physiology; Streptococcus infections; Tumor necrosis factor-α; cytokine; placental macrophage; infection; inflammation; Group B Streptococcus; inflammasome
• ISSN: 1046-7408; 1600-0897
• DOI: 10.1111/aji.13075

Problem During pregnancy, Group B Streptococcus (GBS) can infect fetal membranes to cause chorioamnionitis, resulting in adverse pregnancy outcomes. Macrophages are the primary resident phagocyte in extraplacental membranes. Protein kinase D (PKD) was recently implicated in mediating pro‐inflammatory macrophage responses to GBS outside of the reproductive system. This work aimed to characterize the human placental macrophage inflammatory response to GBS and address the extent to which PKD mediates such effects. Method Primary human placental macrophages were infected with GBS in the presence or absence of a specific, small molecule PKD inhibitor, CRT 0066101. Macrophage phenotypes were characterized by evaluating gene expression, cytokine release, assembly of the NLRP3 inflammasome, and NFκB activation. Results GBS evoked a strong inflammatory phenotype characterized by the release of inflammatory cytokines (TNFα, IL‐1β, IL‐6 (P ≤ 0.05), NLRP3 inflammasome assembly (P ≤ 0.0005), and NFκB activation (P ≤ 0.05). Pharmacological inhibition of PKD suppressed these responses, newly implicating a role for PKD in mediating immune responses of primary human placental macrophages to GBS. Conclusion PKD plays a critical role in mediating placental macrophage inflammatory activation in response to GBS infection.