Colony-Stimulating Factor-1-Dependent Macrophage Functions Regulate the Maternal Decidua Immune Responses against<i>Listeria monocytogenes</i>Infections during Early Gestation in Mice

Qiu, Xuan; Zhu, Liyin; Pollard, Jeffrey W.

doi:10.1128/iai.01022-08

Cited by 29 publications

(26 citation statements)

References 61 publications

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“…Singh et al (58) indeed reported that decidual Mf were highly capable of recognizing and phagocytosing bacteria. Further supporting this notion, M-CSF-deficient mice were more susceptible to pregnancy loss caused by Listeria monocytogenes infection (59), and IL-10-deficient mice were more susceptible to fetal loss induced by LPS (60,61) and the TLR9 ligand CpG (62), as compared with wild-type mice. Thus, these results indicate a crucial role for decidual Mf, not only in supporting an antiinflammatory environment, but also in the protection of the fetus against invading pathogens and infections, which, if uncontrolled, might cause spontaneous abortions or preterm labor.…”

Section: Discussionsupporting

confidence: 60%

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

Svensson

Jenmalm

Matussek

et al. 2011

The Journal of Immunology

315

314

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During pregnancy, the maternal immune system is challenged by the presence of the fetus, which must be tolerated despite being semiallogeneic. Uterine mucosal (or decidual) macrophages (Mϕ), one of the major leukocyte populations at the fetal–maternal interface, have been implicated in fetal tolerance, but information regarding their regulation is scarce. In this study, we investigated the role of several factors potentially involved in the differentiation and polarization of decidual Mϕ with an in vitro Mϕ differentiation model. By using flow cytometry, we showed that M-CSF and IL-10 were potent inducers of M2 (immunoregulatory) Mϕ markers expressed on human decidual Mϕ (CD14, CD163, CD206, CD209). In contrast, proinflammatory stimuli, and unexpectedly also the Th2-associated IL-4 and IL-13, induced different patterns of expression, indicating that a Th2-dominated environment is not required for decidual Mϕ polarization. M-CSF/IL-10–stimulated and decidual Mϕ also showed similar cytokine secretion patterns, with production of IL-10 as well as IL-6, TNF, and CCL4. Conversely, the proinflammatory, LPS/IFN-γ–stimulated Mϕ produced significantly higher levels of TNF and no IL-10. We also used a gene array with 420 Mϕ-related genes, of which 100 were previously reported to be regulated in a global gene expression profiling of decidual Mϕ, confirming that M-CSF/IL-10–induced Mϕ are closely related to decidual Mϕ. Taken together, our results consistently point to a central role for M-CSF and in particular IL-10 in the shaping of decidual Mϕ with regulatory properties. These cytokines may therefore play an important role in supporting the homeostatic and tolerant immune milieu required for a successful pregnancy.

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Section: Discussionsupporting

confidence: 60%

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

Svensson

Jenmalm

Matussek

et al. 2011

The Journal of Immunology

315

314

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“…The relevance of these cytokines in pregnancy is further supported by their increased levels at the fetal-maternal interface (37,43), as well as by observations of increased rates of spontaneous abortions in M-CSF-deficient mice (44) and in mice with a local defect in IL-10 production (45). In addition, both M-CSF-deficient mice (46) and IL-10-deficient mice (47,48) show increased susceptibility to infection-induced fetal loss. Thus, it is likely that placental-derived M-CSF and IL-10 promote macro- + T cells exposed to 6.25% PE CM was partially reversed by the addition of neutralizing Abs against TGF-b (C), IL-10R (D), or TRAIL (E).…”

Section: Foxp3mentioning

confidence: 99%

The Human Fetal Placenta Promotes Tolerance against the Semiallogeneic Fetus by Inducing Regulatory T Cells and Homeostatic M2 Macrophages

Svensson‐Arvelund

Mehta

Lindau

et al. 2015

The Journal of Immunology

261

247

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A successful pregnancy requires that the maternal immune system is instructed to a state of tolerance to avoid rejection of the semiallogeneic fetal-placental unit. Although increasing evidence supports that decidual (uterine) macrophages and regulatory T cells (Tregs) are key regulators of fetal tolerance, it is not known how these tolerogenic leukocytes are induced. In this article, we show that the human fetal placenta itself, mainly through trophoblast cells, is able to induce homeostatic M2 macrophages and Tregs. Placental-derived M-CSF and IL-10 induced macrophages that shared the CD14(+)CD163(+)CD206(+)CD209(+) phenotype of decidual macrophages and produced IL-10 and CCL18 but not IL-12 or IL-23. Placental tissue also induced the expansion of CD25(high)CD127(low)Foxp3(+) Tregs in parallel with increased IL-10 production, whereas production of IFN-gamma (Th1), IL-13 (Th2), and IL-17 (Th17) was not induced. Tregs expressed the suppressive markers CTLA-4 and CD39, were functionally suppressive, and were induced, in part, by IL-10, TGF-beta, and TRAIL. Placental-derived factors also limited excessive Th cell activation, as shown by decreased HLA-DR expression and reduced secretion of Th1-, Th2-, and Th17-associated cytokines. Thus, our data indicate that the fetal placenta has a central role in promoting the homeostatic environment necessary for successful pregnancy. These findings have implications for immune-mediated pregnancy complications, as well as for our general understanding of tissue-induced tolerance.

Funding Agencies|Medical Research Council [K2013-61X-22310-01-4]

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“…The early stage of the host response in the decidua is particularly important because preexisting maternal adaptive T cell immunity does not protect the maternal-fetal interface from infection with L. monocytogenes (23). Interestingly, pregnant CSF-1 mutant op/op mice, which lack macrophages, and artificially decidualized macrophage-depleted mice show increased L. monocytogenes burdens within the placenta and uterus at 2 to 3 days postinfection, raising the possibility that macrophages control L. monocytogenes within the pregnant uterus (24). However, given that L. monocytogenes traffics from the maternal spleen and liver to the uterus (25), these results may be secondary to increases in the splenic or hepatic listerial burden.…”

mentioning

confidence: 99%

Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis

et al. 2017

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The bacterial pathogen Listeria monocytogenes causes foodborne systemic disease in pregnant women, which can lead to preterm labor, stillbirth, or severe neonatal disease. Colonization of the maternal decidua appears to be an initial step in the maternal component of the disease as well as bacterial transmission to the placenta and fetus. Host-pathogen interactions in the decidua during this early stage of infection remain poorly understood. Here, we assessed the dynamics of L. monocytogenes infection in primary human decidual organ cultures and in the murine decidua in vivo. A high inoculum was necessary to infect both human and mouse deciduas, and the data support the existence of a barrier to initial colonization of the murine decidua. If successful, however, colonization in both species was followed by significant bacterial expansion associated with an inability of the decidua to mount appropriate innate cellular immune responses. The innate immune deficits included the failure of bacterial foci to attract macrophages and NK cells, cell types known to be important for early defenses against L. monocytogenes in the spleen, as well as a decrease in the tissue density of inflammatory Ly6C hi monocytes in vivo. These results suggest that the infectivity of the decidua is not the result of an enhanced recruitment of L. monocytogenes to the gestational uterus but rather is due to compromised local innate cellular immune responses.KEYWORDS Listeria monocytogenes, decidua, placenta T he pregnant uterus is a dynamic organ that supports fetoplacental growth, with many trophic functions provided by the decidua, the specialized endometrial tissue that encases the conceptus (1). The decidua also provides a unique immunological environment that blocks the maternal immune system from recognizing the conceptus as a foreign tissue and rejecting it as if it were a solid-organ transplant (2). As a consequence, this environment would be expected to provide opportunities for pathogens to infect the maternal-fetal interface. Indeed, infection of the decidua is now considered to be a critical first step in the hematogenous transmission of a variety of pathogens from mother to fetus (3-7). One such organism is the facultative, intracellular, Gram-positive bacterium Listeria monocytogenes, a clinically relevant foodborne pathogen that can cause severe disease in pregnant women. Once L. monocytogenes reaches the placenta, there are increased risks of severe maternal disease and pregnancy complications, including preterm labor and devastating fetal/neonatal morbidity and mortality (8, 9).Because of its experimental tractability, L. monocytogenes is an excellent model

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Colony-Stimulating Factor-1-Dependent Macrophage Functions Regulate the Maternal Decidua Immune Responses againstListeria monocytogenesInfections during Early Gestation in Mice

Cited by 29 publications

References 61 publications

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

The Human Fetal Placenta Promotes Tolerance against the Semiallogeneic Fetus by Inducing Regulatory T Cells and Homeostatic M2 Macrophages

Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis

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