000168378 001__ 168378
000168378 005__ 20260204153543.0
000168378 0247_ $$2doi$$a10.3389/fmicb.2025.1682405
000168378 0248_ $$2sideral$$a147870
000168378 037__ $$aART-2025-147870
000168378 041__ $$aeng
000168378 100__ $$aFonseca-Perez, Monica Selena
000168378 245__ $$aPhysiological stage-dependent effects of Mycobacterium tuberculosis on human placental tissue: insights into early reactivation and immune modulation
000168378 260__ $$c2025
000168378 5060_ $$aAccess copy available to the general public$$fUnrestricted
000168378 5203_ $$aBackground: Tuberculosis (TB) poses a significant risk during pregnancy and the postpartum period, with evidence linking these stages to an increased likelihood of progression from latent TB infection to active disease. Although TB has been associated with adverse pregnancy outcomes, including congenital transmission, the mechanisms by which Mycobacterium tuberculosis (Mtb) affects placental structure and function remain poorly understood. Objective: This study aimed to investigate the stage-dependent effects of Mtb infection on human placental tissue and assess the potential for vertical transmission using an ex vivo placental infection model. Methods: Human term placental explants were infected ex vivo with Mtb H37Rv in logarithmic (log) phase and in reactivated dormancy phases (rNRP1 and rNRP2). Bacterial viability was evaluated by CFU quantification at 4, 24, and 48 h post-infection. Histological changes were assessed with hematoxylin-eosin staining; bacilli were visualized using Kinyoun staining and immunofluorescence. Cytokine secretion was measured via multiplex ELISA assays, and Mtb gene expression was analyzed by RT-qPCR. Results: Mtb in rNRP1 and rNRP2 phases replicated efficiently within placental explants, with CFU increasing by more than one log at 48 h. rNRP2 exhibited delayed tissue entry (only 4% at 24 h), suggesting distinct virulence dynamics based on bacterial phase. Both reactivated phases induced villitis, stromal fibrosis, and reduced vascular integrity, with rNRP2 causing the most severe tissue damage. rpfB was significantly upregulated during reactivation (14-fold in rNRP1, 7-fold in rNRP2 at 24 h). Dormancy genes (dosR, hspX, icl1) and stress-response markers (sigH, whiB3), were over-expressed in rNRP1, suggesting Mtb remain metabolically equipped to withstand host stresses during early reactivation. Cytokine analysis revealed lower pro-inflammatory responses in rNRP1-infected tissue, while rNRP2 and log-phase Mtb triggered stronger metalloproteinase activity. Conclusion: Mtb can infect, persist, and replicate within human placental tissue, compromising its structural and immune integrity. These effects vary with the bacterial physiological phase, with early-reactivated Mtb showing the greatest capacity for tissue dissemination and damage. These findings underscore a dual risk of placental injury and increased potential for vertical transmission during early reactivation, emphasizing the need for timely TB screening and intervention during pregnancy.
000168378 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000168378 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000168378 700__ $$aVillavicencio-Carrisoza, Oscar
000168378 700__ $$aGrobeisen-Duque, Orly
000168378 700__ $$aHerrera-Moro-Huitron, Luis Antonio
000168378 700__ $$aFlores-Pliego, Arturo
000168378 700__ $$aEspejel-Nuñez, Aurora
000168378 700__ $$aOlmos-Ortiz, Andrea
000168378 700__ $$adel-Castillo-Hernandez, Belen Betsaida
000168378 700__ $$aRojo-Garcia, Jose Ramon
000168378 700__ $$aRivera-Gutierrez, Sandra
000168378 700__ $$aCerna-Cortes, Jorge Francisco
000168378 700__ $$aZaga-Clavellina, Veronica
000168378 700__ $$aVillegas-Mota, Maria Isabel
000168378 700__ $$aAguilar-Ayala, Diana Angelica$$uUniversidad de Zaragoza
000168378 700__ $$aValdespino-Vazquez, Maria Yolotzin
000168378 700__ $$aHelguera-Repetto, Addy Cecilia
000168378 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología
000168378 773__ $$g16 (2025), 1682405 [22 pp.]$$pFront. microbiol.$$tFrontiers in Microbiology$$x1664-302X
000168378 8564_ $$s7677842$$uhttps://zaguan.unizar.es/record/168378/files/texto_completo.pdf$$yVersión publicada
000168378 8564_ $$s2423933$$uhttps://zaguan.unizar.es/record/168378/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000168378 909CO $$ooai:zaguan.unizar.es:168378$$particulos$$pdriver
000168378 951__ $$a2026-02-04-13:14:50
000168378 980__ $$aARTICLE