Human β‐defensin‐1: A natural antimicrobial peptide present in amniotic fluid that is increased in spontaneous preterm labor with intra‐amniotic infection

Varrey, Aneesha; Romero, Roberto; Panaitescu, Bogdan; Miller, Derek; Chaiworapongsa, Tinnakorn; Patwardhan, Manasi; Faro, Jonathan; Pacora, Percy; Hassan, Sonia S.; Hsu, Chaur‐Dong; Gomez‐Lopez, Nardhy

doi:10.1111/aji.13031

Cited by 41 publications

(28 citation statements)

References 190 publications

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“…In the context of intra-amniotic inflammation, the most abundant leukocytes in the amniotic fluid are neutrophils ( 139 , 140 ), which can be of fetal and/or maternal origin ( 141 , 142 ). These innate immune cells actively participate in the mechanisms of host defense against microbial invasion of the amniotic cavity by releasing cytokines ( 140 ) and anti-microbial molecules ( 143 – 145 ), performing phagocytosis ( 146 ), and forming neutrophil extracellular traps or NETs ( 147 , 148 ). Therefore, it was thought that, in the absence of intra-amniotic inflammation, the cellular component of the amniotic fluid was of limited research value.…”

Section: Innate Lymphoid Cells In the Amniotic Cavitymentioning

confidence: 99%

Innate Lymphoid Cells in the Maternal and Fetal Compartments

et al. 2018

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Pregnancy success is orchestrated by the complex balance between the maternal and fetal immune systems. Herein, we summarize the potential role of innate lymphoid cells (ILCs) in the maternal and fetal compartments. We reviewed published literature describing different ILC subsets [ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer (LTi) cells] in the uterus, decidua, fetal tissues [liver, secondary lymphoid organs (SLO), intestine, and lung] and amniotic cavity. ILC1s, ILC2s, and ILC3s are present in the murine uterus prior to and during pregnancy but have only been detected in the non-pregnant endometrium in humans. Specifically, ILC2s reside in the murine uterus from mid-pregnancy to term, ILC1s increase throughout gestation, and ILC3s remain constant. Yet, LTi cells have only been detected in the non-pregnant murine uterus. In the human decidua, ILC1s, ILC3s, and LTi-like cells are more abundant during early gestation, whereas ILC2s increase at the end of pregnancy. Decidual ILC1s were also detected during mid-gestation in mice. Interestingly, functional decidual ILC2s and ILC3s increased in women who underwent spontaneous preterm labor, indicating the involvement of such cells in this pregnancy complication. Fetal ILCs exist in the liver, SLO, intestine, lung, and amniotic cavity. The fetal liver is thought to be the source of ILC progenitors since the differentiation of these cells from hematopoietic stem cells occurs at this site, and mature ILC subsets can be found in this compartment as well. The interaction between LTi cells and specialized stromal cells is important during the formation of SLO. Mature ILCs are found at the mucosal surfaces of the lung and intestine, from where they can extravasate into the amniotic cavity. Amniotic fluid ILCs express high levels of RORγt, CD161, and CD103, hallmarks of ILC3s. Such cells are more abundant in the second trimester than later in gestation. Although amniotic fluid ILC3s produce IL-17A and TNFα, indicating their functionality, their numbers in patients with intra-amniotic infection/inflammation remain unchanged compared to those without this pregnancy complication. Collectively, these findings suggest that maternal (uterine and decidual) ILCs play central roles in both the initiation and maintenance of pregnancy, and fetal ILCs participate in the development of immunity.

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Section: Innate Lymphoid Cells In the Amniotic Cavitymentioning

confidence: 99%

Innate Lymphoid Cells in the Maternal and Fetal Compartments

et al. 2018

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“…Women with clinical chorioamnionitis at term and intra-amniotic infection have high numbers of amniotic fluid immune cells [108], which are more likely to be of maternal origin or a mixture of both fetal and maternal neutrophils [110]. These neutrophils actively participate in the mechanisms of host defense in the amniotic cavity by releasing cytokines [108] and anti-microbial molecules [111][112][113], performing phagocytosis [114], and forming neutrophil extracellular traps [115,116]. In addition, women with clinical chorioamnionitis at term and intra-amniotic infection present severe acute inflammatory lesions in the placenta [40,46,85,117], suggesting that both amniotic fluid neutrophils and the chorioamniotic membranes are a source of extracellular ASC in the amniotic cavity.…”

Section: In Vivo Evidence Of Inflammasome Activation In Clinical Chormentioning

confidence: 99%

Clinical chorioamnionitis at term IX: in vivo evidence of intra-amniotic inflammasome activation

Gomez‐Lopez

Romero

Maymon

et al. 2018

Journal of Perinatal Medicine

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Background The inflammasome has been implicated in the mechanisms that lead to spontaneous labor at term. However, whether the inflammasome is activated in the amniotic cavity of women with clinical chorioamnionitis at term is unknown. Herein, by measuring extracellular ASC [apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (CARD)], we investigated whether there is in vivo inflammasome activation in amniotic fluid of patients with clinical chorioamnionitis at term with sterile intra-amniotic inflammation and in those with intra-amniotic infection. Methods This was a retrospective cross-sectional study that included amniotic fluid samples collected from 76 women who delivered after spontaneous term labor with diagnosed clinical chorioamnionitis. Intra-amniotic inflammation was defined as an elevated amniotic fluid interleukin (IL)-6 concentration ≥2.6 ng/mL, and intra-amniotic infection was diagnosed by the presence of microbial invasion of the amniotic cavity (MIAC) accompanied by intra-amniotic inflammation. Patients were classified into the following groups: (1) women without intra-amniotic inflammation or infection (n=16); (2) women with MIAC but without intra-amniotic inflammation (n=5); (3) women with sterile intra-amniotic inflammation (n=15); and (4) women with intra-amniotic infection (n=40). As a readout of in vivo inflammasome activation, extracellular ASC was measured in amniotic fluid by enzyme-linked immunosorbent assay. Acute inflammatory responses in the amniotic fluid and placenta were also evaluated. Results In clinical chorioamnionitis at term: (1) amniotic fluid concentrations of ASC (extracellular ASC is indicative of in vivo inflammasome activation) and IL-6 were greater in women with intra-amniotic infection than in those without intra-amniotic inflammation, regardless of the presence of MIAC; (2) amniotic fluid concentrations of ASC and IL-6 were also higher in women with sterile intra-amniotic inflammation than in those without intra-amniotic inflammation, regardless of the presence of MIAC; (3) amniotic fluid concentrations of IL-6, but not ASC, were more elevated in women with intra-amniotic infection than in those with sterile intra-amniotic inflammation; (4) a positive and significant correlation was observed between amniotic fluid concentrations of ASC and IL-6; (5) no differences were observed in amniotic fluid ASC and IL-6 concentrations between women with and without MIAC in the absence of intra-amniotic inflammation; (6) women with intra-amniotic infection had elevated white blood cell counts and reduced glucose levels in amniotic fluid compared to the other three study groups; and (7) women with intra-amniotic infection presented higher frequencies of acute maternal and fetal inflammatory responses in the placenta than those with sterile intra-amniotic inflammation. Conclusion The intra-amniotic inflammatory response, either induced by alarmins or microbes, is characterized by the activation of the inflammasome – as evidenced by elevated amniotic fluid concentrations of extracellular ASC – in women with clinical chorioamnionitis at term. These findings provide insight into the intra-amniotic inflammatory response in women with clinical chorioamnionitis at term.

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“…To date, the most studied causes of pathological inflammation leading to preterm labor have been (a) intra‐amniotic infection/inflammation resulting from microbial invasion of the amniotic cavity and (b) intra‐amniotic inflammation without detectable microorganisms (ie, sterile intra‐amniotic inflammation) identified by using both molecular and conventional microbiological techniques, proposed to be due to endogenous danger signals, or alarmins . Most research concerning inflammation‐induced preterm labor has therefore focused on the innate limb of immunity . Yet, several studies reported strong evidence that T cells, the primary cellular component of the adaptive immune system, are present at the maternal‐fetal interface .…”

Section: Introductionmentioning

confidence: 99%

Are B cells altered in the decidua of women with preterm or term labor?

Leng

Romero²,

et al. 2019

American J Rep Immunol

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Problem The immunophenotype of B cells at the maternal‐fetal interface (decidua) in labor at term and preterm labor is poorly understood. Method of study Decidual tissues were obtained from women with preterm or term labor and from non‐labor gestational age‐matched controls. Immunophenotyping of decidual B cells was performed using multicolor flow cytometry. Results (a) In the absence of acute or chronic chorioamnionitis, total B cells were more abundant in the decidua parietalis of women who delivered preterm than in those who delivered at term, regardless of the presence of labor; (b) decidual transitional and naïve B cells were the most abundant B‐cell subsets; (c) decidual B1 B cells were increased in women with either labor at term or preterm labor and chronic chorioamnionitis compared to those without this placental lesion; (d) decidual transitional B cells were reduced in women with preterm labor compared to those without labor; (e) naïve, class‐switched, and non–class‐switched B cells in the decidual tissues underwent mild alterations with the process of preterm labor; (f) decidual plasmablasts seemed to increase in women with either labor at term or preterm labor with chronic chorioamnionitis; and (g) decidual B cells expressed high levels of interleukin (IL)‐12, IL‐6, and/or IL‐35. Conclusion Total B cells are not increased with the presence of preterm or term labor; yet, specific subsets (B1 and plasmablasts) undergo alterations in women with chronic chorioamnionitis. Therefore, B cells are solely implicated in the pathological process of preterm labor in a subset of women with chronic inflammation of the placenta. These findings provide insight into the immunology of the maternal‐fetal interface in preterm and term labor.

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Human β‐defensin‐1: A natural antimicrobial peptide present in amniotic fluid that is increased in spontaneous preterm labor with intra‐amniotic infection

Cited by 41 publications

References 190 publications

Innate Lymphoid Cells in the Maternal and Fetal Compartments

Innate Lymphoid Cells in the Maternal and Fetal Compartments

Clinical chorioamnionitis at term IX: in vivo evidence of intra-amniotic inflammasome activation

Are B cells altered in the decidua of women with preterm or term labor?

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