Prenatal SARS-CoV-2 Infection Alters Human Milk-Derived Extracellular Vesicles

被引：1

作者：

Chutipongtanate, Somchai ^{[1
]}

Kongsomros, Supasek ^{[1
,2
]}

Cetinkaya, Hatice ^{[1
]}

Zhang, Xiang ^{[1
]}

Kuhnell, Damaris ^{[1
]}

Benefield, Desiree ^{[3
]}

Haffey, Wendy D. ^{[4
]}

Wyder, Michael A. ^{[4
]}

Kwatra, Gaurav ^{[5
,6
]}

Conrey, Shannon C. ^{[1
]}

Burrell, Allison R. ^{[5
]}

Langevin, Scott M. ^{[7
]}

Esfandiari, Leyla ^{[2
]}

Newburg, David S. ^{[1
]}

Greis, Kenneth D. ^{[4
]}

Staat, Mary A. ^{[5
]}

Morrow, Ardythe L. ^{[1
,5
]}

机构：

[1] Univ Cincinnati, Dept Environm & Publ Hlth Sci, Coll Med, Cincinnati, OH 45267 USA

[2] Univ Cincinnati, Dept Biomed Engn, Cincinnati, OH 45267 USA

[3] Univ Cincinnati, Ctr Adv Struct Biol, Dept Mol & Cellular Biosci, Coll Med, Cincinnati, OH 45267 USA

[4] Univ Cincinnati, Dept Canc Biol, Coll Med, Cincinnati, OH 45267 USA

[5] Cincinnati Childrens Hosp, Dept Infect Dis, Med Ctr, Cincinnati, OH 45267 USA

[6] Christian Med Coll & Hosp, Dept Clin Microbiol, Vellore 632004, India

[7] Univ Vermont, Larner Coll Med, Burlington, VT 05405 USA

来源：

CELLS | 2025年 / 14卷 / 04期

基金：

美国国家卫生研究院;

关键词：

COVID-19; exosomes; human milk; microRNAs; proteomics; PROTEOMIC ANALYSIS; BREAST-MILK; EXOSOMES; BOVINE; COLOSTRUM; CELLS;

D O I：

10.3390/cells14040284

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Human milk-derived extracellular vesicles (HMEVs) are key components in breast milk, promoting infant health and development. Maternal conditions could affect HMEV cargo; however, the impact of SARS-CoV-2 infection on HMEVs remains unknown. This study investigated the influence of SARS-CoV-2 infection during pregnancy on postpartum HMEV molecules. The median duration from SARS-CoV-2 test positivity to milk collection was 3 months. After defatting and casein micelle disaggregation, HMEVs were isolated from milk samples of nine mothers with prenatal SARS-CoV-2 and six controls by sequential centrifugation, ultrafiltration, and qEV-size exclusion chromatography. The presence of HMEV was confirmed via transmission electron microscopy. Nanoparticle tracking analysis demonstrated particle diameters of <200 nm and yields of >1 x 10(11) particles per mL of milk. Western immunoblots detected ALIX, CD9, and HSP70, supporting the presence of HMEVs in the isolates. Cargo from thousands of HMEVs were analyzed using a multi-omics approach, including proteomics and microRNA sequencing, and predicted that mothers with prenatal SARS-CoV-2 infection produced HMEVs with enhanced functionalities involving metabolic reprogramming, mucosal tissue development, and immunomodulation. Our findings suggest that SARS-CoV-2 infection during pregnancy boosts mucosal site-specific functions of HMEVs, potentially protecting infants against viral infections. Further prospective studies should be pursued to reevaluate the short- and long-term benefits of breastfeeding in the post-COVID era.

引用

页数：15

共 55 条

[1]

Christian P., Smith E.R., Lee S.E., Vargas A.J., Bremer A.A., Raiten D.J., The need to study human milk as a biological system, Am. J. Clin. Nutr, 113, pp. 1063-1072, (2021)

[2]

Meek J.Y., Noble L., Policy Statement: Breastfeeding and the Use of Human Milk, Pediatrics, 150, (2022)

[3]

Videholm S., Wallby T., Silfverdal S.A., Breastfeeding practice, breastfeeding policy and hospitalisations for infectious diseases in early and later childhood: A register-based study in Uppsala County, Sweden, BMJ Open, 11, (2021)

[4]

Oddy W.H., Kendall G.E., Li J., Jacoby P., Robinson M., de Klerk N.H., Silburn S.R., Zubrick S.R., Landau L.I., Stanley F.J., The long-term effects of breastfeeding on child and adolescent mental health: A pregnancy cohort study followed for 14 years, J. Pediatr, 156, pp. 568-574, (2010)

[5]

Chutipongtanate S., Morrow A.L., Newburg D.S., Human Milk Extracellular Vesicles: A Biological System with Clinical Implications, Cells, 11, (2022)

[6]

Galley J.D., Besner G.E., The Therapeutic Potential of Breast Milk-Derived Extracellular Vesicles, Nutrients, 12, (2020)

[7]

Zempleni J., Aguilar-Lozano A., Sadri M., Sukreet S., Manca S., Wu D., Zhou F., Mutai E., Biological Activities of Extracellular Vesicles and Their Cargos from Bovine and Human Milk in Humans and Implications for Infants, J. Nutr, 147, pp. 3-10, (2017)

[8]

Wolf T., Baier S.R., Zempleni J., The Intestinal Transport of Bovine Milk Exosomes Is Mediated by Endocytosis in Human Colon Carcinoma Caco-2 Cells and Rat Small Intestinal IEC-6 Cells, J. Nutr, 145, pp. 2201-2206, (2015)

[9]

Manca S., Upadhyaya B., Mutai E., Desaulniers A.T., Cederberg R.A., White B.R., Zempleni J., Milk exosomes are bioavailable and distinct microRNA cargos have unique tissue distribution patterns, Sci. Rep, 8, (2018)

[10]

Sadri M., Shu J., Kachman S.D., Cui J., Zempleni J., Milk exosomes and miRNA cross the placenta and promote embryo survival in mice, Reproduction, 160, pp. 501-509, (2020)

← 1 2 3 4 5 6 →