The human placenta dictates the phenotype of decidual macrophages.

Pollheimer, J.; Vondra, S.; Hoebler, A.-L.; Lackner, A. I.; Raffetseder, J.; Mihalic, Z. N.; Saleh, L.; Kunihs, V.; Haslinger, P.; Wahrmann, M.; Husslein, H.; Oberle, R.; Kargl, J.; Haider, S.; Latos, P.; Knoefler, M.; Ernerudh, J.

doi:10.1101/2022.03.29.486171

bioRxiv · 10.1101/2022.03.29.486171

The human placenta dictates the phenotype of decidual macrophages.

Pollheimer, J.·Vondra, S.·Hoebler, A.-L.·Lackner, A. I.·Raffetseder, J.·Mihalic, Z. N.·Saleh, L.·Kunihs, V.·Haslinger, P.·Wahrmann, M.·Husslein, H.·Oberle, R.·Kargl, J.·Haider, S.·Latos, P.·Knoefler, M.·Ernerudh, J.

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Abstract

During human pregnancy, placenta-derived extravillous trophoblasts (EVT) invade the decidua and communicate with maternal immune cells. The decidua can be distinguished into basalis (decB) and parietalis (decP), the latter being unaffected by placentation. By defining a novel gating strategy, we report accumulation of myeloid cells in decB. We identified a decidua basalis-associated macrophage (decBAM) population with a differential transcriptome and secretome when compared to decidua parietalis-associated macrophages (decPAMs). decBAMs are CD11chi and efficient inducers of Tregs, proliferate in situ and secrete high levels of CXCL1, CXCL5, M-CSF, and IL-10. In contrast, decPAMs exert a dendritic cell-like, motile phenotype characterized by induced expression of HLA class II molecules, enhanced phagocytosis, and the ability to activate T cells. Strikingly, EVT-conditioned media are able to convert decPAMs into a decBAM phenotype. Cumulatively, these findings assign distinct macrophage phenotypes to decidual areas depending on placentation and further highlight a critical role for EVTs in the induction of pregnancy-tolerant macrophage polarization. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/486171v3_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@130f55dorg.highwire.dtl.DTLVardef@13cad47org.highwire.dtl.DTLVardef@942b9forg.highwire.dtl.DTLVardef@1bbe575_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsIn this study, we identified so far unrecognized, placenta-induced immune responses at the maternal-fetal interface. Altogether, we imply that placenta-derived trophoblasts induce a pregnancy-tolerant phenotype by suppressing antigen-presenting cell-like functions in maternal tissue macrophages.

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Pollheimer, J., Vondra, S., Hoebler, A.-L., Lackner, A. I., Raffetseder, J., Mihalic, Z. N., Saleh, L., Kunihs, V., Haslinger, P., Wahrmann, M., Husslein, H., Oberle, R., Kargl, J., Haider, S., Latos, P., Knoefler, M., Ernerudh, J.. 2022-03-30. The human placenta dictates the phenotype of decidual macrophages.. https://doi.org/10.1101/2022.03.29.486171

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