Lactobacillus crispatus FY121-Derived Extracellular Vesicles Suppress HPV-Positive Cervical Cancer Cells and Activate RIG-I/MAVS/IRF3 Signaling
- 1Department of Microbiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China
- 2Heilongjiang Province Key Laboratory of Immunity & Infection, Harbin 150081, China
- 3Virology Laboratory, Harbin Center for Disease Control and Prevention, Harbin 150056, China
Abstract
High-risk human papillomavirus (HPV) infection is the major cause of cervical cancer (CC), and viral oncogenes E6 and E7 contribute to tumor progression by promoting malignant transformation and impairing innate immune responses. Extracellular vesicles (EVs) derived from beneficial bacteria have emerged as potential regulators of host cellular functions. However, their role in HPV-associated cervical cancer remains unclear. In this study, we isolated and characterized extracellular vesicles derived from Lactobacillus crispatus FY121 (LcEVs) and investigated their effects on HPV-positive cervical cancer cell lines. LcEVs were efficiently internalized by HPV16-positive SiHa and HPV18-positive HeLa cells and significantly suppressed cell proliferation, migration, and invasion. Furthermore, LcEVs reduced HPV E6 and E7 expression at both the transcriptional and protein levels. Mechanistically, LcEV treatment was associated with increased RIG-I/MAVS/IRF3 signaling and enhanced IFN-β transcription and secretion. Transcriptomic analysis further revealed broad alterations in immune-related and cellular functional programs following LcEV treatment. In a co-injection xenograft model, LcEVs reduced tumor establishment and early outgrowth of HPV-positive cervical cancer cells and were accompanied by increased RIG-I/MAVS/IRF3 signaling in tumor tissue. Proteomic profiling identified diverse functional proteins within LcEVs, providing potential molecular candidates underlying their biological effects. Together, these results show that LcEVs suppress the malignant phenotypes of HPV-positive cervical cancer cells and are accompanied by activation of nucleic acid sensing and type I interferon signaling in vitro and in vivo. The identity of the active vesicular cargo and its causal contribution to these effects remain to be established, and bacterial EVs are highlighted as candidate immunomodulatory agents for HPV-related malignancies.
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BibTeX
@article{cao2026lactobacillus,
title = {{Lactobacillus crispatus FY121-Derived Extracellular Vesicles Suppress HPV-Positive Cervical Cancer Cells and Activate RIG-I/MAVS/IRF3 Signaling}},
author = {Guoding Cao and Shuang Liang and Meng Yuan and Chongyao Xue and Mingyang Ding and Luyi Li and Yong Fang},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16111560},
url = {https://www.mdpi.com/2218-273X/16/11/1560},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Lactobacillus crispatus FY121-Derived Extracellular Vesicles Suppress HPV-Positive Cervical Cancer Cells and Activate RIG-I/MAVS/IRF3 Signaling
AU - Guoding Cao
AU - Shuang Liang
AU - Meng Yuan
AU - Chongyao Xue
AU - Mingyang Ding
AU - Luyi Li
AU - Yong Fang
PY - 2026
DA - 2026/10/26
JO - Biomolecules
DO - 10.3390/biom16111560
UR - https://www.mdpi.com/2218-273X/16/11/1560
AB - High-risk human papillomavirus (HPV) infection is the major cause of cervical cancer (CC), and viral oncogenes E6 and E7 contribute to tumor progression by promoting malignant transformation and impairing innate immune responses. Extracellular vesicles (EVs) derived from beneficial bacteria have emerged as potential regulators of host cellular functions. However, their role in HPV-associated cervical cancer remains unclear. In this study, we isolated and characterized extracellular vesicles derived from Lactobacillus crispatus FY121 (LcEVs) and investigated their effects on HPV-positive cervical cancer cell lines. LcEVs were efficiently internalized by HPV16-positive SiHa and HPV18-positive HeLa cells and significantly suppressed cell proliferation, migration, and invasion. Furthermore, LcEVs reduced HPV E6 and E7 expression at both the transcriptional and protein levels. Mechanistically, LcEV treatment was associated with increased RIG-I/MAVS/IRF3 signaling and enhanced IFN-β transcription and secretion. Transcriptomic analysis further revealed broad alterations in immune-related and cellular functional programs following LcEV treatment. In a co-injection xenograft model, LcEVs reduced tumor establishment and early outgrowth of HPV-positive cervical cancer cells and were accompanied by increased RIG-I/MAVS/IRF3 signaling in tumor tissue. Proteomic profiling identified diverse functional proteins within LcEVs, providing potential molecular candidates underlying their biological effects. Together, these results show that LcEVs suppress the malignant phenotypes of HPV-positive cervical cancer cells and are accompanied by activation of nucleic acid sensing and type I interferon signaling in vitro and in vivo. The identity of the active vesicular cargo and its causal contribution to these effects remain to be established, and bacterial EVs are highlighted as candidate immunomodulatory agents for HPV-related malignancies.
SN - 2218-273X
ER -