Longitudinal expression of Toll-like receptors on dendritic cells in uncomplicated pregnancy and postpartum

• Published in: American journal of obstetrics and gynecology 2014-05, Vol.210 (5), p.445.e1-445.e6
• Main Authors: Young, Brett C., MD, Stanic, Aleksandar K., MD, PhD, Panda, Britta, MD, PhD, Rueda, Bo R., PhD, Panda, Alexander, MD, PhD, MPH
• Format: Article
• Language: English
• Subjects: dendritic cells; Dendritic Cells - immunology; Female; Humans; innate immune system; Interferon-alpha - metabolism; Interleukin-12 - metabolism; Interleukin-6 - metabolism; Obstetrics and Gynecology; Postpartum Period - immunology; Postpartum Period - physiology; pregnancy; Pregnancy - immunology; Pregnancy - metabolism; Prospective Studies; toll-like receptors; Toll-Like Receptors - metabolism; Toll-Like Receptors - physiology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2013.11.037

Objective Toll-like receptors (TLRs) are integral parts of the innate immune system and have been implicated in complications of pregnancy. The longitudinal expression of TLRs on dendritic cells in the maternal circulation during uncomplicated pregnancies is unknown. The objective of this study was to prospectively evaluate TLRs 1-9 as expressed on dendritic cells in the maternal circulation at defined intervals throughout pregnancy and postpartum. Study Design This was a prospective cohort of 30 pregnant women with uncomplicated pregnancies and 30 nonpregnant controls. TLRs and cytokine expression was measured in unstimulated dendritic cells at 4 defined intervals during pregnancy and postpartum. Basal expression of TLRs and cytokines was measured by multicolor flow cytometry. The percent-positive dendritic cells for each TLRs were compared with both nonpregnant and postpartum levels with multivariate linear regression. Results TLRs 1, 7, and 9 were elevated compared with nonpregnant controls with persistent elevation of TLR 1 and interleukin-12 (IL-12) into the postpartum period. Concordantly, levels of IL-6, IL-12, interferon alpha, and tumor necrosis factor alpha increased during pregnancy and returned to levels similar to nonpregnant controls during the postpartum period. The elevated levels of TLR 1 and IL-12 were persistent postpartum, challenging notions that immunologic changes during pregnancy resolve after the prototypical postpartum period. Conclusion Normal pregnancy is associated with time-dependent changes in TLR expression compared with nonpregnant controls; these findings may help elucidate immunologic dysfunction in complicated pregnancies.