Distinct maternofetal immune signatures delineate preterm birth onset following urinary tract infection.

Autor:	Ottinger S; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA., Larson AB; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA., Mercado-Evans V; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.; Medical Scientist Training Program, Baylor College of Medicine., Branthoover H; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA., Zulk JJ; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA., Serchejian C; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA., Mejia ME; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA., Hameed ZA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA., Walde R; Department of Pathology, University of South Alabama, Mobile, Alabama, USA., Fleck RC; Department of Microbiology and Immunology, University of South Alabama., Shea AE; Department of Microbiology and Immunology, University of South Alabama., Patras KA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.; Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Oct 25. Date of Electronic Publication: 2024 Oct 25.
DOI:	10.1101/2024.10.22.619711
Abstrakt:	Preterm birth is the leading cause of infant mortality resulting in over one million neonatal deaths annually. Maternal urinary tract infection (UTI) during pregnancy increases risk for preterm birth; however, biological processes mediating UTI-associated preterm birth are not well-described. We established a murine maternal UTI model in which challenge with uropathogenic E. coli resulted in preterm birth in about half of dams. Dams experiencing preterm birth displayed excessive bladder inflammation and altered uteroplacental T cell polarization compared to non-laboring infected dams, with no differences in bacterial burdens. Additional factors associated with preterm birth included higher proportions of male fetuses and lower maternal serum IL-10. Furthermore, exogenous maternal IL-10 treatment absolved UTI-associated preterm birth but contributed to fetal growth restriction in this model. Using urine samples from a cohort of human pregnancies with or without UTI, we correlated urinary cytokines with birth outcomes and urine culture status. These analyses yielded a non-invasive, highly predictive three-model system for evaluating preterm birth risk implicating cytokines IL-10, IL-15, IL-1β, and IL-1RA. Our unique bimodal murine model coupled with patient samples provides a platform to investigate immunological and microbial factors governing UTI-associated preterm birth, revealing novel therapeutic opportunities to predict or prevent preterm birth. Competing Interests: Conflict of interest statement: The authors have declared that no conflict of interest exists.
Databáze:	MEDLINE
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