Browsing by Author "Tarca, Adi L."

Now showing 1 - 20 of 25
  • No Thumbnail Available
    Item
    A key role for NLRP3 signaling in preterm labor and birth driven by the alarmin S100B
    (2023) Galaz, Jose; Motomura, Kenichiro; Romero, Roberto; Liu, Zhenjie; Garcia-Flores, Valeria; Tao, Li; Xu, Yi; Done, Bogdan; Arenas-Hernandez, Marcia; Kanninen, Tomi; Farias-Jofre, Marcelo; Miller, Derek; Tarca, Adi L.; Gomez-Lopez, Nardhy
    Preterm birth remains the leading cause of neonatal morbidity and mortality worldwide. A substantial number of spontaneous preterm births occur in the context of sterile intra-amniotic inflammation, a condition that has been mechanistically proven to be triggered by alarmins. However, sterile intra-amniotic inflammation still lacks treatment. The NLRP3 inflammasome has been implicated in sterile intra-amniotic inflammation; yet, its underlying mechanisms, as well as the maternal and fetal contributions to this signaling pathway, are unclear. Herein, by utilizing a translational and clinically relevant model of alarmin-induced preterm labor and birth in Nlrp3-/- mice, we investigated the role of NLRP3 signaling by using imaging and molecular biology approaches. Nlrp3 deficiency abrogated preterm birth and the resulting neonatal mortality induced by the alarmin S100B by impeding the premature activation of the common pathway of labor as well as by dampening intra-amniotic and fetal inflammation. Moreover, Nlrp3 deficiency altered leukocyte infiltration and functionality in the uterus and decidua. Last, embryo transfer revealed that maternal and fetal Nlrp3 signaling contribute to alarmin-induced preterm birth and neonatal mortality, further strengthening the concept that both individuals participate in the complex process of preterm parturition. These findings provide novel insights into sterile intra-amniotic inflammation, a common etiology of preterm labor and birth, suggesting that the adverse perinatal outcomes resulting from prematurity can be prevented by targeting NLRP3 signaling.
  • Thumbnail Image
    Item
    A role for microRNAs - Key regulators of gene expression - In chorioamnionitis and parturition
    (2006) Montenegro, Daniel; Romero, Roberto; Pineles, Beth L.; Tarca, Adi L.; Kim, Yeon Mee; Draghici, Sorin; Kusanovic, Juan Pedro; Erez, Offer; Mazakitovi, Shali; Hassan, Sonia; Espinoza, Jimmy; Kim, Chong Jai
  • No Thumbnail Available
    Item
    A single-cell atlas of murine reproductive tissues during preterm labor
    (2023) Garcia-Flores, Valeria; Romero, Roberto; Peyvandipour, Azam; Galaz, Jose; Pusod, Errile; Panaitescu, Bogdan; Miller, Derek; Xu, Yi; Tao, Li; Liu, Zhenjie; Tarca, Adi L.; Pique-Regi, Roger; Gomez-Lopez, Nardhy
    Preterm birth, the leading cause of perinatal morbidity and mortality worldwide, frequently results from the syndrome of preterm labor. The best-established causal link to preterm labor is intra-amniotic infection, which involves premature activation of the parturition cascade in the reproductive tissues. Herein, we utilize single-cell RNA sequencing (scRNA-seq) to generate a single-cell atlas of the murine uterus, decidua, and cervix in a model of infection-induced preterm labor. We show that preterm labor affects the transcriptomic profiles of specific immune and non-immune cell subsets. Shared and tissue-specific gene expression sig-natures are identified among affected cells. Determination of intercellular communications implicates spe-cific cell types in preterm labor-associated signaling pathways across tissues. In silico comparison of murine and human uterine cell-cell interactions reveals conserved signaling pathways implicated in labor. Thus, our scRNA-seq data provide insights into the preterm labor-driven cellular landscape and communications in reproductive tissues.
  • Thumbnail Image
    Item
    Characterization of the Fetal Blood Transcriptome and Proteome in Maternal Anti-Fetal Rejection: Evidence of a Distinct and Novel Type of Human Fetal Systemic Inflammatory Response
    (2013) Lee, JoonHo; Romero, Roberto; Chaiworapongsa, Tinnakorn; Dong, Zhong; Tarca, Adi L.; Xu, Yu; Chiang, Po Jen; Kusanovic, Juan Pedro; Hassan, Sonia S.; Yeo, Lami; Yoon, Bo Hyun; Than, Nandor Gabor; Kim, Chong Jai
  • Thumbnail Image
    Item
    Characterization of visceral and subcutaneous adipose tissue transcriptome and biological pathways in pregnant and non-pregnant women : evidence for pregnancy-related regional-specific differences in adipose tissue
    (2015) Mazaki-Tovi, Shali; Vaisbuch, Edi; Tarca, Adi L.; Kusanovic, Juan Pedro; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Dong, Zhong; Hassan, Sonia S.; Romero, Roberto
  • Thumbnail Image
    Item
  • Thumbnail Image
    Item
    Clinical chorioamnionitis at term II : the intra-amniotic inflammatory response
    (2016) Romero, Roberto; Chaemsaithong, Piya; Steven J. Korzeniewski; Tarca, Adi L.; Bhatti, Gaurav; Xu, Zhonghui; Kusanovic, Juan Pedro
  • No Thumbnail Available
    Item
    Clinical chorioamnionitis at term II: The intra-amniotic inflammatory response
    (2016) Romero, Roberto; Chaemsaithong, Piya; Korzeniewski, Steven J.; Tarca, Adi L.; Bhatti, Gaurav; Xu, Zhonghui; Kusanovic, Juan Pedro; Dong, Zhong; Docheva, Nikolina; Martínez Varea, Alicia; Yoon, Bo Hyun; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn; Yeo, Lami
    Objective: Recent studies indicate that clinical chorioamnionitis is a heterogeneous condition and only approximately one-half of the patients have bacteria in the amniotic cavity, which is often associated with intra-amniotic inflammation. The objective of this study is to characterize the nature of the inflammatory response within the amniotic cavity in patients with clinical chorioamnionitis at term according to the presence or absence of 1) bacteria in the amniotic cavity and 2) intra-amniotic inflammation. Materials and methods: A retrospective cross-sectional case-control study was conducted to examine cytokine and chemokine concentrations in the amniotic fluid (AF). Cases consisted of women with clinical chorioamnionitis at term (n=45). Controls were women with uncomplicated pregnancies at term who did not have intra-amniotic inflammation and were in labor (n=24). Women with clinical chorioamnionitis were classified according to the results of AF cultures, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry, and AF concentration of interleukin-6 (IL-6) into those: 1) without intra-amniotic inflammation, 2) with microbial-associated intra-amniotic inflammation, and 3) with intra-amniotic inflammation without detectable bacteria. The AF concentrations of 29 cytokines/chemokines were determined using sensitive and specific V-PLEX immunoassays. Results: 1) The AF concentrations of pro- and anti-inflammatory cytokines/chemokines such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-4 (IL-4), macrophage inflammatory protein-1 beta (MIP-1β), and interleukin-8 (IL-8) (except Eotaxin-3) were significantly higher in women with clinical chorioamnionitis at term than in controls (term labor without intra-amniotic inflammation); 2) patients with microbial-associated intra-amniotic inflammation, and those with intra-amniotic inflammation without detectable bacteria, had a dramatic differential expression of cytokines and chemokines in AF compared to patients with spontaneous labor without intra-amniotic inflammation. However, no difference could be detected in the pattern of the intra-amniotic inflammatory response between patients with intra-amniotic inflammation with and without detectable bacteria; and 3) in patients with clinical chorioamnionitis at term but without intra-amniotic inflammation, the behavior of cytokines and chemokines in the AF was similar to those in spontaneous labor at term. Conclusions: Patients with clinical chorioamnionitis who had microbial-associated intra-amniotic inflammation or intra-amniotic inflammation without detectable bacteria had a dramatic upregulation of the intra-amniotic inflammatory response assessed by amniotic fluid concentrations of cytokines. A subset of patients with term clinical chorioamnionitis does not have intra-amniotic infection/inflammation, as demonstrated by elevated AF concentrations of inflammation-related proteins, when compared to women in term labor with uncomplicated pregnancies, suggesting over-diagnosis. These observations constitute the first characterization of the cytokine/chemokine network in the amniotic cavity of patients with clinical chorioamnionitis at term.
  • Thumbnail Image
    Item
    Clinical chorioamnionitis at term IX : in vivo evidence of intra-amniotic inflammasome activation
    (2019) Gomez-López, Nardhy; Romero, Roberto; Maymon, Ely; Kusanovic, Juan Pedro; Panaitescu, Bogdan; Miller, Derek; Pacora, Percy; Tarca, Adi L.; Motomura, Kenichiro; Erez, Offer; Jung, Eunjung J.; Hassan, Sonia S.; Hsu, Chaur Dong
  • No Thumbnail Available
    Item
    Deciphering maternal-fetal cross-talk in the human placenta during parturition using single-cell RNA sequencing
    (2024) Garcia-Flores, Valeria; Romero, Roberto; Tarca, Adi L.; Peyvandipour, Azam; Xu, Yi; Galaz, Jose; Miller, Derek; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Berry, Stanley M.; Awonuga, Awoniyi O.; Bryant, David R.; Pique-Regi, Roger; Gomez-Lopez, Nardhy
    Labor is a complex physiological process requiring a well-orchestrated dialogue between the mother and fetus. However, the cellular contributions and communications that facilitate maternal-fetal cross-talk in labor have not been fully elucidated. Here, single-cell RNA sequencing (scRNA-seq) was applied to decipher maternal-fetal signaling in the human placenta during term labor. First, a single-cell atlas of the human placenta was established, demonstrating that maternal and fetal cell types underwent changes in transcriptomic activity during labor. Cell types most affected by labor were fetal stromal and maternal decidual cells in the chorioamniotic membranes (CAMs) and maternal and fetal myeloid cells in the placenta. Cell-cell interaction analyses showed that CAM and placental cell types participated in labor-driven maternal and fetal signaling, including the collagen, C-X-C motif ligand (CXCL), tumor necrosis factor (TNF), galectin, and interleukin-6 (IL-6) pathways. Integration of scRNA-seq data with publicly available bulk transcriptomic data showed that placenta-derived scRNA-seq signatures could be monitored in the maternal circulation throughout gestation and in labor. Moreover, comparative analysis revealed that placenta-derived signatures in term labor were mirrored by those in spontaneous preterm labor and birth. Furthermore, we demonstrated that early in gestation, labor-specific, placenta-derived signatures could be detected in the circulation of women destined to undergo spontaneous preterm birth, with either intact or prelabor ruptured membranes. Collectively, our findings provide insight into the maternal-fetal cross-talk of human parturition and suggest that placenta-derived single-cell signatures can aid in the development of noninvasive biomarkers for the prediction of preterm birth.
  • Thumbnail Image
    Item
    Detection of Anti-HLA Antibodies in Maternal Blood in the Second Trimester to Identify Patients at Risk of Antibody-Mediated Maternal Anti-Fetal Rejection and Spontaneous Preterm Delivery
    (2013) Lee, JoonHo; Romero, Roberto; Xu, Yi; Miranda, Jezid; Yoo, Wonsuk; Chaemsaithong, Piya; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Tarca, Adi L.; Korzeniewski, Steven J.; Hassan, Sonia S.; Than, Nandor Gabor; Yoon, Bo Hyun; Kim, Chong Jai
  • Thumbnail Image
    Item
    Differential immunophenotype of circulating monocytes from pregnant women in response to viral ligands
    (2023) Farías Jofré, Marcelo Enrique; Romero, Roberto; Xu, Yi; Levenson, Dustyn; Tao, Li; Kanninen, Tomi; Galaz, Jose; Arenas-Hernandez, Marcia; Liu, Zhenjie; Miller, Derek; Bhatti, Gaurav; Seyerle, Megan; Tarca, Adi L.; Gomez-Lopez, Nardhy
    Background Viral infections during pregnancy can have deleterious effects on mothers and their offspring. Monocytes participate in the maternal host defense against invading viruses; however, whether pregnancy alters monocyte responses is still under investigation. Herein, we undertook a comprehensive in vitro study of peripheral monocytes to characterize the differences in phenotype and interferon release driven by viral ligands between pregnant and non-pregnant women. Methods Peripheral blood was collected from third-trimester pregnant (n = 20) or non-pregnant (n = 20, controls) women. Peripheral blood mononuclear cells were isolated and exposed to R848 (TLR7/TLR8 agonist), Gardiquimod (TLR7 agonist), Poly(I:C) (HMW) VacciGrade™ (TLR3 agonist), Poly(I:C) (HMW) LyoVec™ (RIG-I/MDA-5 agonist), or ODN2216 (TLR9 agonist) for 24 h. Cells and supernatants were collected for monocyte phenotyping and immunoassays to detect specific interferons, respectively. Results The proportions of classical (CD14hiCD16−), intermediate (CD14hiCD16+), non-classical (CD14loCD16+), and CD14loCD16− monocytes were differentially affected between pregnant and non-pregnant women in response to TLR3 stimulation. The proportions of pregnancy-derived monocytes expressing adhesion molecules (Basigin and PSGL-1) or the chemokine receptors CCR5 and CCR2 were diminished in response to TLR7/TLR8 stimulation, while the proportions of CCR5− monocytes were increased. Such differences were found to be primarily driven by TLR8 signaling, rather than TLR7. Moreover, the proportions of monocytes expressing the chemokine receptor CXCR1 were increased during pregnancy in response to poly(I:C) stimulation through TLR3, but not RIG-I/MDA-5. By contrast, pregnancy-specific changes in the monocyte response to TLR9 stimulation were not observed. Notably, the soluble interferon response to viral stimulation by mononuclear cells was not diminished in pregnancy. Conclusions Our data provide insight into the differential responsiveness of pregnancy-derived monocytes to ssRNA and dsRNA, mainly driven by TLR8 and membrane-bound TLR3, which may help to explain the increased susceptibility of pregnant women to adverse outcomes resulting from viral infection as observed during recent and historic pandemics.
  • Thumbnail Image
    Item
    Distinct Cellular Immune Responses to SARS-CoV-2 in Pregnant Women
    (2022) Gomez-Lopez, Nardhy ; Romero, Roberto ; Tao, Li ; Gershater, Meyer ; Leng, Yaozhu ; Zou, Chengrui; Farias-Jofre, Marcelo ; Galaz, Jose ; Miller, Derek; Tarca, Adi L. ; Arenas-Hernandez, Marcia ; Bhatti, Gaurav; Garcia-Flores, Valeria ; Liu, Zhenjie ; Para, Robert ; Kanninen, Tomi ; Hadaya, Ola ; Paredes, Carmen ; Xu, Yi
  • No Thumbnail Available
    Item
    Exhausted and Senescent T Cells at the Maternal-Fetal Interface in Preterm and Term Labor
    (2019) Slutsky, Rebecca; Romero, Roberto; Xu, Yi; Galaz, Jose; Miller, Derek; Done, Bogdan; Tarca, Adi L.; Gregor, Sabrina; Hassan, Sonia S.; Leng, Yaozhu; Gomez-Lopez, Nardhy
    Successful pregnancy requires a tightly-regulated equilibrium of immune cell interactions at the maternal-fetal interface (i.e., the decidual tissues), which plays a central role in the inflammatory process of labor. Most of the innate immune cells in this compartment have been well characterized; however, adaptive immune cells are still under investigation. Herein, we performed immunophenotyping of the decidua basalis and decidua parietalis to determine whether exhausted and senescent T cells are present at the maternal-fetal interface and whether the presence of pathological (i.e., preterm) or physiological (i.e., term) labor and/or placental inflammation alter such adaptive immune cells. In addition, decidual exhausted T cells were sorted to test their functional status. We found that (1) exhausted and senescent T cells were present at the maternal-fetal interface and predominantly expressed an effector memory phenotype, (2) exhausted CD4(+) T cells increased in the decidua parietalis as gestational age progressed, (3) exhausted CD4(+) and CD8(+) T cells decreased in the decidua basalis of women who underwent labor at term compared to those without labor, (4) exhausted CD4(+) T cells declined with the presence of placental inflammation in the decidua basalis of women with preterm labor, (5) exhausted CD8(+) T cells decreased with the presence of placental inflammation in the decidua basalis of women who underwent labor at term, (6) both senescent CD4(+) and CD8(+) T cells declined with the presence of placental inflammation in the decidua basalis of women who underwent preterm labor, and (7) decidual exhausted T cells produced IFN and TNF upon in vitro stimulation. Collectively, these findings indicate that exhausted and senescent T cells are present at the human maternal-fetal interface and undergo alterations in a subset of women either with labor at term or preterm labor and placental inflammation. Importantly, decidual T cell function can be restored upon stimulation.
  • Thumbnail Image
    Item
    Fetal and maternal NLRP3 signaling is required for preterm labor and birth
    (AMER SOC CLINICAL INVESTIGATION INC, 2022) Motomura, Kenichiro; Romero, Roberto; Galaz, Jose; Tao, Li; Garcia-Flores, Valeria; Xu, Yi; Done, Bogdan; Arenas-Hernandez, Marcia; Miller, Derek; Gutierrez-Contreras, Pedro; Farias-Jofre, Marcelo; Aras, Siddhesh; Grossman, Lawrence, I; Tarca, Adi L.; Gomez-Lopez, Nardhy
    Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. One of every 4 preterm neonates is born to a mother with intra-amniotic inflammation driven by invading bacteria. However, the molecular mechanisms underlying this hostile immune response remain unclear. Here, we used a translationally relevant model of preterm birth in Nlrp3-deficient and-sufficient pregnant mice to identify what we believe is a previously unknown dual role for the NLRP3 pathway in the fetal and maternal signaling required for the premature onset of the labor cascade leading to fetal injury and neonatal death. Specifically, the NLRP3 sensor molecule and/or inflammasome is essential for triggering intra-amniotic and decidual inflammation, fetal membrane activation, uterine contractility, and cervical dilation. NLRP3 also regulates the functional status of neutrophils and macrophages in the uterus and decidua, without altering their influx, as well as maternal systemic inflammation. Finally, both embryo transfer experimentation and heterozygous mating systems provided mechanistic evidence showing that NLRP3 signaling in both the fetus and the mother is required for the premature activation of the labor cascade. These data provide insights into the mechanisms of fetal-maternal dialog in the syndrome of preterm labor and indicate that targeting the NLRP3 pathway could prevent adverse perinatal outcomes.
  • No Thumbnail Available
    Item
    Immunosequencing and Profiling of T Cells at the Maternal-Fetal Interface of Women with Preterm Labor and Chronic Chorioamnionitis
    (2023) Miller, Derek; Romero, Roberto; Myers, Luke; Xu, Yi; Arenas-Hernández, Marcia; Galáz Alarcón, José Carlo; Soto, Cinque; Done, Bogdan; Quiroz, Angélica; Awonuga, Awoniyi O.; Bryant, David R.; Tarca, Adi L.; Gómez-Lopez, Nardhy
    T cells are implicated in the pathophysiology of preterm labor and birth, the leading cause of neonatal morbidity and mortality worldwide. Specifically, maternal decidual T cells infiltrate the chorioamniotic membranes in chronic chorioamnionitis (CCA), a placental lesion considered to reflect maternal anti-fetal rejection, leading to preterm labor and birth. However, the phenotype and TCR repertoire of decidual T cells in women with preterm labor and CCA have not been investigated. In this study, we used phenotyping, TCR sequencing, and functional assays to elucidate the molecular characteristics and Ag specificity of T cells infiltrating the chorioamniotic membranes in women with CCA who underwent term or preterm labor. Phenotyping indicated distinct enrichment of human decidual effector memory T cell subsets in cases of preterm labor with CCA without altered regulatory T cell proportions. TCR sequencing revealed that the T cell repertoire of CCA is characterized by increased TCR richness and decreased clonal expansion in women with preterm labor. We identified 15 clones associated with CCA and compared these against established TCR databases, reporting that infiltrating T cells may possess specificity for maternal and fetal Ags, but not common viral Ags. Functional assays demonstrated that choriodecidual T cells can respond to maternal and fetal Ags. Collectively, our findings provide, to our knowledge, novel insight into the complex processes underlying chronic placental inflammation and further support a role for effector T cells in the mechanisms of disease for preterm labor and birth. Moreover, this work further strengthens the contribution of adaptive immunity to the syndromic nature of preterm labor and birth.
  • No Thumbnail Available
    Item
    Immunosequencing and Profiling of T Cells at the Maternal-Fetal Interface of Women with Preterm Labor and Chronic Chorioamnionitis
    (Springer, 2023) Miller, Derek; Romero, Roberto; Myers, Luke; Xu, Yi; Arenas-Hernández, Marcia; Galáz Alarcón, José Carlo; Soto, Cinque; Done, Bogdan; Quiroz, Angélica; Awonuga, Awoniyi O.; Bryant, David R.; Tarca, Adi L.; Gómez-Lopez, Nardhy; CEDEUS (Chile)
    T cells are implicated in the pathophysiology of preterm labor and birth, the leading cause of neonatal morbidity and mortality worldwide. Specifically, maternal decidual T cells infiltrate the chorioamniotic membranes in chronic chorioamnionitis (CCA), a placental lesion considered to reflect maternal anti-fetal rejection, leading to preterm labor and birth. However, the phenotype and TCR repertoire of decidual T cells in women with preterm labor and CCA have not been investigated. In this study, we used phenotyping, TCR sequencing, and functional assays to elucidate the molecular characteristics and Ag specificity of T cells infiltrating the chorioamniotic membranes in women with CCA who underwent term or preterm labor. Phenotyping indicated distinct enrichment of human decidual effector memory T cell subsets in cases of preterm labor with CCA without altered regulatory T cell proportions. TCR sequencing revealed that the T cell repertoire of CCA is characterized by increased TCR richness and decreased clonal expansion in women with preterm labor. We identified 15 clones associated with CCA and compared these against established TCR databases, reporting that infiltrating T cells may possess specificity for maternal and fetal Ags, but not common viral Ags. Functional assays demonstrated that choriodecidual T cells can respond to maternal and fetal Ags. Collectively, our findings provide, to our knowledge, novel insight into the complex processes underlying chronic placental inflammation and further support a role for effector T cells in the mechanisms of disease for preterm labor and birth. Moreover, this work further strengthens the contribution of adaptive immunity to the syndromic nature of preterm labor and birth.
  • No Thumbnail Available
    Item
    Immunosequencing and Profiling of T Cells at the Maternal-Fetal Interface of Women with Preterm Labor and Chronic Chorioamnionitis
    (2023) Miller, Derek; Romero, Roberto; Myers, Luke; Xu, Yi; Arenas-Hernández, Marcia; Galáz Alarcón, José Carlo; Soto, Cinque; Done, Bogdan; Quiroz, Angélica; Awonuga, Awoniyi O.; Bryant, David R.; Tarca, Adi L.; Gómez-Lopez, Nardhy
    T cells are implicated in the pathophysiology of preterm labor and birth, the leading cause of neonatal morbidity and mortality worldwide. Specifically, maternal decidual T cells infiltrate the chorioamniotic membranes in chronic chorioamnionitis (CCA), a placental lesion considered to reflect maternal anti-fetal rejection, leading to preterm labor and birth. However, the phenotype and TCR repertoire of decidual T cells in women with preterm labor and CCA have not been investigated. In this study, we used phenotyping, TCR sequencing, and functional assays to elucidate the molecular characteristics and Ag specificity of T cells infiltrating the chorioamniotic membranes in women with CCA who underwent term or preterm labor. Phenotyping indicated distinct enrichment of human decidual effector memory T cell subsets in cases of preterm labor with CCA without altered regulatory T cell proportions. TCR sequencing revealed that the T cell repertoire of CCA is characterized by increased TCR richness and decreased clonal expansion in women with preterm labor. We identified 15 clones associated with CCA and compared these against established TCR databases, reporting that infiltrating T cells may possess specificity for maternal and fetal Ags, but not common viral Ags. Functional assays demonstrated that choriodecidual T cells can respond to maternal and fetal Ags. Collectively, our findings provide, to our knowledge, novel insight into the complex processes underlying chronic placental inflammation and further support a role for effector T cells in the mechanisms of disease for preterm labor and birth. Moreover, this work further strengthens the contribution of adaptive immunity to the syndromic nature of preterm labor and birth.
  • Thumbnail Image
    Item
    Pregnancy imparts distinct systemic adaptive immune function
    (WILEY, 2022) Demery-Poulos, Catherine; Romero, Roberto; Xu, Yi; Arenas-Hernandez, Marcia; Miller, Derek; Tao, Li; Galaz, Jose; Farias-Jofre, Marcelo; Bhatti, Gaurav; Garcia-Flores, Valeria; Seyerle, Megan; Tarca, Adi L.; Gomez-Lopez, Nardhy
    Problem Pregnancy represents a state of systemic immune activation that is primarily driven by alterations in circulating innate immune cells. Recent studies have suggested that cellular adaptive immune components, T cells and B cells, also undergo changes throughout gestation. However, the phenotypes and functions of such adaptive immune cells are poorly understood. Herein, we utilized high-dimensional flow cytometry and functional assays to characterize T-cell and B-cell responses in pregnant and non-pregnant women. Methods Peripheral blood mononuclear cells from pregnant (n = 20) and non-pregnant (n = 25) women were used for phenotyping of T-cell and B-cell subsets. T-cell proliferation and B-cell activation were assessed by flow cytometry after in vitro stimulation, and lymphocyte cytotoxicity was evaluated by using a cell-based assay. Statistical comparisons were performed with linear mixed-effects models. Results Pregnancy was associated with modestly enhanced basal activation of peripheral CD4(+) T cells. Both CD4(+) and CD8(+) T cells from pregnant women showed increased activation-induced proliferation; yet, a reduced proportion of these cells expressed activation markers compared to non-pregnant women. There were no differences in peripheral lymphocyte cytotoxicity between study groups. A greater proportion of B cells from pregnant women displayed memory-like and activated phenotypes, and such cells exhibited higher activation following stimulation. Conclusion Maternal circulating T cells and B cells display distinct responses during pregnancy. The former may reflect the unique capacity of T cells to respond to potential threats without undergoing aberrant activation, thereby preventing systemic inflammatory responses that can lead to adverse perinatal consequences.
  • Thumbnail Image
    Item
    Pregnancy tailors endotoxin-induced monocyte and neutrophil responses in the maternal circulation
    (SPRINGER BASEL AG, 2022) Farias-Jofre, Marcelo; Romero, Roberto; Galaz, Jose; Xu, Yi; Tao, Li; Demery-Poulos, Catherine; Arenas-Hernandez, Marcia; Bhatti, Gaurav; Liu, Zhenjie; Kawahara, Naoki; Kanninen, Tomi; Shaffer, Zachary; Chaiworapongsa, Tinnakorn; Theis, Kevin R.; Tarca, Adi L.; Gomez-Lopez, Nardhy
    Objective To comprehensively characterize monocyte and neutrophil responses to E. coli and its product [lipopolysaccharide (LPS) or endotoxin] in vitro during pregnancy.