*4.1.3.3. Chorioamnionitis*

During pregnancy, placenta could be the target of infectious agents. The chorioamnionitis, mainly due to ascending polymicrobial infection, is a severe complication of the pregnancy leading to an acute inflammation of the membrane and chorion [143]. In human placenta, we observed a decreased number of macrophages expressing CD14, CD68 and CD163 in at term placentas from women with chorioamnionitis compared to placenta from normal pregnancies [127]. Our results are in agreement with other reports [144, 145]. In addition, isolated macrophages from placenta with chorioamnionitis exhibit an altered inflammatory response with decreased production of IL-10 [127]. Other reports describe a M2 profile of macrophages from chorioamnionitis placentas [146]. These findings underline the role of placenta macrophages in the control of infection in pregnant women.

### **4.2. Dendritic cells**

Dendritic cells are found at the feto-maternal interface and in decidua basalis [147]. They represent approximately 2% of leukocytes from placenta and their number does not vary through gestation. Both mature dendritic cells (expressing CD83) and immature dendritic cells (expressing CD14 and DC-SIGN) have been identified in placenta tissue [148]. We previously isolated decidual dendritic cells from at term placentas of healthy women by combining negative selection with anti-CD14 antibodies and positive selection with anti-CD11c antibodies [149]. We found that 1525 genes are differentially modulated with a specific transcriptional profile as compared to monocyte-derived dendritic cells. It mainly consists of the up-modulation of genes involved in immunomodulatory cytokines, estrogen and progesterone gene pathway. The investigation of gene expression programs in placenta dendritic cells is emerging and will require additional investigation to associate gene expression and dendritic cells subsets in normal and pathological pregnancy.

### **4.3. Mast cells**

preeclamptic placentas [132]. The transcriptomic and protein expression of CD74, a HLA class II molecule, are decreased in placental macrophages of preeclampsia women. This down-regulation of CD74 interferes with trophoblast-macrophage cross-talk [138]. Prins et al. investigated macrophages in early decidua from women who later developed preeclampsia [139]. They observed an increased expression of CD68 mRNA, but decreased CD206/CD68 mRNA ratio, suggesting that the number of M2 macrophages is affected before the onset of preeclampsia. This finding may be related to the increased number of M1 macrophages in preeclamptic placenta found by other authors [140]. A better comprehension of the rupture of the M1/M2 balance may provide insight into understanding of preeclampsia pathogenesis.

The inflammation associated with GDM leads to macrophage infiltration into placenta, suggesting a key role of these cells during this metabolic complication of pregnancy. The number of macrophages is increased in placentas from women with GDM as compared to normal pregnancy [141]. Placental macrophages, isolated from an experimental model of diabetes (rats receiving an injection of streptozotocin), change from M2 to M1 inflammatory profile under high glucose stimulation [142]. Similarly, isolated placental macrophages from diabetic women present a M1 or an atypical M2 profile [142]. Immunohistochemistry and PCR approaches show that the mRNA expression levels of TNF and IL-6 are higher in placentas from women with GDM than in controls, suggesting an inflammatory profile of placenta macrophages. Further studies are needed to define the role of inflammatory macrophages

During pregnancy, placenta could be the target of infectious agents. The chorioamnionitis, mainly due to ascending polymicrobial infection, is a severe complication of the pregnancy leading to an acute inflammation of the membrane and chorion [143]. In human placenta, we observed a decreased number of macrophages expressing CD14, CD68 and CD163 in at term placentas from women with chorioamnionitis compared to placenta from normal pregnancies [127]. Our results are in agreement with other reports [144, 145]. In addition, isolated macrophages from placenta with chorioamnionitis exhibit an altered inflammatory response with decreased production of IL-10 [127]. Other reports describe a M2 profile of macrophages from chorioamnionitis placentas [146]. These findings underline the role of placenta macrophages

Dendritic cells are found at the feto-maternal interface and in decidua basalis [147]. They represent approximately 2% of leukocytes from placenta and their number does not vary through gestation. Both mature dendritic cells (expressing CD83) and immature dendritic cells (expressing CD14 and DC-SIGN) have been identified in placenta tissue [148].

*4.1.3.2. Gestational diabetes mellitus*

in GDM.

42 Placenta

*4.1.3.3. Chorioamnionitis*

**4.2. Dendritic cells**

in the control of infection in pregnant women.

Mast cells are found in human placentas [150] and it has been reported that mast cells and their products, especially histamine, could participate in the placenta development. Indeed, histamine is involved in trophoblast invasion and growth [151] and the cross-talk with trophoblasts *via* the expression of adhesion molecules by trophoblasts [152]. The alteration of these specific adhesion molecules is associated with the impairment of placenta invasion and the outcome of preeclampsia. A decreased number of mast cells have been reported in preeclampsia, GDM and intrauterine growth retardation [151, 153]. To our knowledge, no data about gene expression in placenta mast cells has been published. We isolated placenta mast cells from at term women using positive selection with CD117 and IgE antibodies. In a comparative study with a mast cell line (human mast cells, HMC-1.2), we found that a large number of genes are up-modulated in placenta mast cells. The functional analysis reveals an enrichment with three categories, FcεRI signaling, immune response and reproduction processes. In this latter category, we identified specific genes of Wnt pathway and a set of genes involved in the response to estrogen and progesterone (manuscript in preparation). These preliminary results highlight the originality of placenta mast cells among placenta innate immune cells.
