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Protein kinase D mediates inflammatory responses of human placental macrophages to Group B Streptococcus
Author(s) -
Sutton Jessica A.,
Rogers Lisa M.,
Dixon Beverly R.E.A.,
Kirk Leslie,
Doster Ryan,
Algood Holly M.,
Gaddy Jennifer A.,
Flaherty Rebecca,
Manning Shan D.,
Aronoff David M.
Publication year - 2019
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.13075
Subject(s) - inflammasome , chorioamnionitis , macrophage , biology , immunology , streptococcus agalactiae , cytokine , inflammation , proinflammatory cytokine , macrophage inflammatory protein , fetal membrane , placenta , streptococcus , interleukin , fetus , pregnancy , in vitro , biochemistry , genetics , bacteria
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.