Browsing by Author "Galaz Alarcón, José Carlo"

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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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    M2-polarized macrophages prevent preterm birth and improve neonatal survival and immunity
    (AMER ASSOC IMMUNOLOGISTS, 2024) Garcia-Flores, Valeria; Liu, Zhenjie; Romero, Roberto; Xu, Yi; Miller, Derek; Galaz Alarcón, José Carlo; Winters, Andrew; Farías Jofre, Marcelo Enrique; Theis, Kevin; Gomez-Lopez, Nardhy
    Preterm birth (PTB), commonly preceded by preterm labor, is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm labor are associated with sterile intra-amniotic inflammation (SIAI), an inflammatory condition without detectable microorganisms. To date, no successful strategies to treat SIAI have been developed. Herein, we present mechanistic proof that treatment with M2-polarized macrophages (M2 MΦ) can effectively prevent PTB [(HMGB1, n = 28 vs. HMGB1+M2 MΦ, n = 29) (p<0.05)] and neonatal mortality [(HMGB1, n = 20 litters vs. HMGB1+M2 MΦ, n = 14 litters) (p<0.001)] induced by the ultrasound-guided intra-amniotic injection of the alarmin HMGB1 in mice. M2 MΦ halt the premature pathway of labor by infiltrating maternal and fetal compartments, where they inhibit NLRP3 inflammasome activation triggered by HMGB1. Furthermore, M2 MΦ dampen the HMGB1-induced inflammatory response in the amniotic cavity and fetal lung. Notably, neonates exposed to HMGB1 in utero display a reduced capacity to clear bacterial infection and gut microbiome dysbiosis, which are restored by M2 MΦ treatment [(HMGB1, n = 10 vs. HMGB1+ M2 MΦ, n = 10) (p<0.001 and p<0.01, respectively)]. Our findings provide cogent evidence that M2 MΦ can serve as a cellular strategy to mitigate PTB and decrease neonatal mortality.
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    Pregnancy-specific responses to COVID-19 are revealed by high-throughput proteomics of human plasma
    (2022) Gomez-Lopez, Nardhy; Romero, Roberto; Escobar, Maria; Carvajal, Javier; Echavarria, Maria; Albornoz, Ludwig; Nasner, Daniela; Miller, Derek; Gallo, Dahiana; Galaz Alarcón, José Carlo; Arenas-Hernandez, Marcia; Bhatti, Gaurav; Done, Bogdan; Zambrano, Maria; Ramos, Isabella; Fernandez, Paula; Posada, Leandro; Chaiworapongsa, Tinnakorn; Jung, Eunjung; Garcia-Flores, Valeria; Suksai, Manaphat; Gotsch, Francesca; Bosco, Mariachiara; Than, Nandor; Tarca, Adi