TY - JOUR
T1 - Specific innate immune cells uptake fetal antigen and display homeostatic phenotypes in the maternal circulation
AU - Arenas-Hernandez, Marcia
AU - Romero, Roberto
AU - Gershater, Meyer
AU - Tao, Li
AU - Xu, Yi
AU - Garcia-Flores, Valeria
AU - Pusod, Errile
AU - Miller, Derek
AU - Galaz, Jose
AU - Motomura, Kenichiro
AU - Schwenkel, George
AU - Para, Robert
AU - Gomez-Lopez, Nardhy
N1 - Publisher Copyright:
© 2021 Society for Leukocyte Biology
PY - 2022/3
Y1 - 2022/3
N2 - Pregnancy represents a period when the mother undergoes significant immunological changes to promote tolerance of the fetal semi-allograft. Such tolerance results from the exposure of the maternal immune system to fetal antigens (Ags), a process that has been widely investigated at the maternal-fetal interface and in the adjacent draining lymph nodes. However, the peripheral mechanisms of maternal-fetal crosstalk are poorly understood. Herein, we hypothesized that specific innate immune cells interact with fetal Ags in the maternal circulation. To test this hypothesis, a mouse model was utilized in which transgenic male mice expressing the chicken ovalbumin (OVA) Ag under the beta-actin promoter were allogeneically mated with wild-type females to allow for tracking of the fetal Ag. Fetal Ag-carrying Ly6G+ and F4/80+ cells were identified in the maternal circulation, where they were more abundant in the second half of pregnancy. Such innate immune cells displayed unique phenotypes: while Ly6G+ cells expressed high levels of MHC-II and CD80 together with low levels of pro-inflammatory cytokines, F4/80+ cells up-regulated the expression of CD86 as well as the anti-inflammatory cytokines IL-10 and TGF-β. In vitro studies using allogeneic GFP+ placental particles revealed that maternal peripheral Ly6G+ and F4/80+ cells phagocytose fetal Ags in mid and late murine pregnancy. Importantly, cytotrophoblast-derived particles were also engulfed in vitro by CD15+ and CD14+ cells from women in the second and third trimester, providing translational evidence that this process also occurs in humans. Collectively, this study demonstrates novel interactions between specific maternal circulating innate immune cells and fetal Ags, thereby shedding light on the systemic mechanisms of maternal-fetal crosstalk.
AB - Pregnancy represents a period when the mother undergoes significant immunological changes to promote tolerance of the fetal semi-allograft. Such tolerance results from the exposure of the maternal immune system to fetal antigens (Ags), a process that has been widely investigated at the maternal-fetal interface and in the adjacent draining lymph nodes. However, the peripheral mechanisms of maternal-fetal crosstalk are poorly understood. Herein, we hypothesized that specific innate immune cells interact with fetal Ags in the maternal circulation. To test this hypothesis, a mouse model was utilized in which transgenic male mice expressing the chicken ovalbumin (OVA) Ag under the beta-actin promoter were allogeneically mated with wild-type females to allow for tracking of the fetal Ag. Fetal Ag-carrying Ly6G+ and F4/80+ cells were identified in the maternal circulation, where they were more abundant in the second half of pregnancy. Such innate immune cells displayed unique phenotypes: while Ly6G+ cells expressed high levels of MHC-II and CD80 together with low levels of pro-inflammatory cytokines, F4/80+ cells up-regulated the expression of CD86 as well as the anti-inflammatory cytokines IL-10 and TGF-β. In vitro studies using allogeneic GFP+ placental particles revealed that maternal peripheral Ly6G+ and F4/80+ cells phagocytose fetal Ags in mid and late murine pregnancy. Importantly, cytotrophoblast-derived particles were also engulfed in vitro by CD15+ and CD14+ cells from women in the second and third trimester, providing translational evidence that this process also occurs in humans. Collectively, this study demonstrates novel interactions between specific maternal circulating innate immune cells and fetal Ags, thereby shedding light on the systemic mechanisms of maternal-fetal crosstalk.
KW - human
KW - innate immune cells
KW - maternal-fetal tolerance
KW - mice
KW - OVA
KW - peripheral blood
KW - pregnancy
UR - http://www.scopus.com/inward/record.url?scp=85121393768&partnerID=8YFLogxK
U2 - 10.1002/JLB.5HI0321-179RR
DO - 10.1002/JLB.5HI0321-179RR
M3 - Article
C2 - 34889468
AN - SCOPUS:85121393768
SN - 0741-5400
VL - 111
SP - 519
EP - 538
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 3
ER -