Browsing by Author "Theis, Kevin"

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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.