Browsing by Author "Panzer, Jonathan J."

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    Homeostatic Macrophages Prevent Preterm Birth and Improve Neonatal Outcomes by Mitigating In Utero Sterile Inflammation in Mice
    (2024) García-Flores, Valeria; Liu, Zhenjie; Romero, Roberto; Pique-Regi, Roger; Xu, Yi; Miller, Derek; Levenson, Dustyn; Galaz Alarcón, José Carlo; Winters, Andrew D.; Farias Jofré, Marcelo Enrique; Panzer, Jonathan J.; Theis, Kevin R.; Gómez-López, Nardhy
    Copyright © 2024 by The American Association of Immunologists, Inc.Preterm birth (PTB), often preceded by preterm labor, is a major cause of neonatal morbidity and mortality worldwide. Most PTB cases involve intra-amniotic inflammation without detectable microorganisms, termed in utero sterile inflammation, for which there is no established treatment. In this study, we propose homeostatic macrophages to prevent PTB and adverse neonatal outcomes caused by in utero sterile inflammation. Single-cell atlases of the maternal-fetal interface revealed that homeostatic maternal macrophages are reduced with human labor. M2 macrophage treatment prevented PTB and reduced adverse neonatal outcomes in mice with in utero sterile inflammation. Specifically, M2 macrophages halted premature labor by suppressing inflammatory responses in the amniotic cavity, including inflammasome activation, and mitigated placental and offspring lung inflammation. Moreover, M2 macrophages boosted gut inflammation in neonates and improved their ability to fight systemic bacterial infections. Our findings show that M2 macrophages are a promising strategy to mitigate PTB and improve neonatal outcomes resulting from in utero sterile inflammation.
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    Homeostatic Macrophages Prevent Preterm Birth and Improve Neonatal Outcomes by Mitigating In Utero Sterile Inflammation in Mice
    (2024) García-Flores, Valeria; Liu, Zhenjie; Romero, Roberto; Pique-Regi, Roger; Xu, Yi; Miller, Derek; Levenson, Dustyn; Galaz Alarcón, José Carlo; Winters, Andrew D.; Farias Jofré, Marcelo Enrique; Panzer, Jonathan J.; Theis, Kevin R.; Gómez-López, Nardhy
    Preterm birth (PTB), often preceded by preterm labor, is a major cause of neonatal morbidity and mortality worldwide. Most PTB cases involve intra-amniotic inflammation without detectable microorganisms, termed in utero sterile inflammation, for which there is no established treatment. In this study, we propose homeostatic macrophages to prevent PTB and adverse neonatal outcomes caused by in utero sterile inflammation. Single-cell atlases of the maternal-fetal interface revealed that homeostatic maternal macrophages are reduced with human labor. M2 macrophage treatment prevented PTB and reduced adverse neonatal outcomes in mice with in utero sterile inflammation. Specifically, M2 macrophages halted premature labor by suppressing inflammatory responses in the amniotic cavity, including inflammasome activation, and mitigated placental and offspring lung inflammation. Moreover, M2 macrophages boosted gut inflammation in neonates and improved their ability to fight systemic bacterial infections. Our findings show that M2 macrophages are a promising strategy to mitigate PTB and improve neonatal outcomes resulting from in utero sterile inflammation.
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    Is there a placental microbiota? A critical review and re-analysis of published placental microbiota datasets
    (2023) Panzer, Jonathan J.; Romero, Roberto; Greenberg, Jonathan M.; Winters, Andrew D.; Galaz, Jose; Gomez-Lopez, Nardhy; Theis, Kevin R.
    The existence of a placental microbiota is debated. The human placenta has historically been considered sterile and microbial colonization was associated with adverse pregnancy outcomes. Yet, recent DNA sequencing investigations reported a microbiota in typical human term placentas. However, this detected microbiota could represent background DNA or delivery-associated contamination. Using fifteen publicly available 16S rRNA gene datasets, existing data were uniformly re-analyzed with DADA2 to maximize comparability. While Amplicon Sequence Variants (ASVs) identified as Lactobacillus, a typical vaginal bacterium, were highly abundant and prevalent across studies, this prevalence disappeared after applying likely  DNA contaminant removal to placentas from term cesarean deliveries. A six-study sub-analysis targeting the 16S rRNA gene V4 hypervariable region demonstrated that bacterial profiles of placental samples and technical controls share principal bacterial ASVs and that placental samples clustered primarily by study origin and mode of delivery. Contemporary DNA-based evidence does not support the existence of a placental microbiota. Importance Early-gestational microbial influences on human development are unclear. By applying DNA sequencing technologies to placental tissue, bacterial DNA signals were observed, leading some to conclude that a live bacterial placental microbiome exists in typical term pregnancy. However, the low-biomass nature of the proposed microbiome and high sensitivity of current DNA sequencing technologies indicate that the signal may alternatively derive from environmental or delivery-associated bacterial DNA contamination. Here we address these alternatives with a re-analysis of 16S rRNA gene sequencing data from 15 publicly available placental datasets. After identical DADA2 pipeline processing of the raw data, subanalyses were performed to control for mode of delivery and environmental DNA contamination. Both environment and mode of delivery profoundly influenced the bacterial DNA signal from term-delivered placentas. Aside from these contamination-associated signals, consistency was lacking across studies. Thus, placentas delivered at term are unlikely to be the original source of observed bacterial DNA signals.
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    The Vaginal Microbiota of Pregnant Women Varies with Gestational Age, Maternal Age, and Parity
    (2023) Romero, Roberto; Theis, Kevin R.; Gomez-Lopez, Nardhy; Winters, Andrew D.; Panzer, Jonathan J.; Lin, Huang; Galaz, Jose; Greenberg, Jonathan M.; Shaffer, Zachary; Kracht, David J.; Chaiworapongsa, Tinnakorn; Jung, Eunjung; Gotsch, Francesca; Ravel, Jacques; Peddada, Shyamal D.; Tarca, Adi L.
    There is debate regarding links between the vaginal microbiota and pregnancy complications, especially spontaneous preterm birth. Inconsistencies in results among studies are likely due to differences in sample sizes and cohort ethnicity.