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Cervical Gene Delivery of the Antimicrobial Peptide, Human β-Defensin (HBD)-3, in a Mouse Model of Ascending Infection-Related Preterm Birth

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Title: Cervical Gene Delivery of the Antimicrobial Peptide, Human β-Defensin (HBD)-3, in a Mouse Model of Ascending Infection-Related Preterm Birth
Authors: Natalie Suff, Rajvinder Karda, Juan Antinao Diaz, Joanne Ng, Julien Baruteau, Dany Perocheau, Peter W. Taylor, Dagmar Alber, Suzanne M. K. Buckley, Mona Bajaj-Elliott, Simon N. Waddington, Donald Peebles
Source: Frontiers in Immunology, Vol 11 (2020)
Publisher Information: Frontiers Media S.A., 2020.
Publication Year: 2020
Collection: LCC:Immunologic diseases. Allergy
Subject Terms: cervix, gene therapy, preterm birth, antimicrobial peptides, ascending infection, Immunologic diseases. Allergy, RC581-607
More Details: Approximately 40% of preterm births are preceded by microbial invasion of the intrauterine space; ascent from the vagina being the most common pathway. Within the cervical canal, antimicrobial peptides and proteins (AMPs) are important components of the cervical barrier which help to prevent ascending vaginal infection. We investigated whether expression of the AMP, human β-defensin-3 (HBD3), in the cervical mucosa of pregnant mice could prevent bacterial ascent from the vagina into the uterine cavity. An adeno-associated virus vector containing both the HBD3 gene and GFP transgene (AAV8 HBD3.GFP) or control AAV8 GFP, was administered intravaginally into E13.5 pregnant mice. Ascending infection was induced at E16.5 using bioluminescent Escherichia coli (E. coli K1 A192PP-lux2). Bioluminescence imaging showed bacterial ascent into the uterine cavity, inflammatory events that led to premature delivery and a reduction in pups born alive, compared with uninfected controls. Interestingly, a significant reduction in uterine bioluminescence in the AAV8 HBD3.GFP-treated mice was observed 24 h post-E. coli infection, compared to AAV8 GFP treated mice, signifying reduced bacterial ascent in AAV8 HBD3.GFP-treated mice. Furthermore, there was a significant increase in the number of living pups in AAV HBD3.GFP-treated mice. We propose that HBD3 may be a potential candidate for augmenting cervical innate immunity to prevent ascending infection-related preterm birth and its associated neonatal consequences.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-3224
Relation: https://www.frontiersin.org/article/10.3389/fimmu.2020.00106/full; https://doaj.org/toc/1664-3224
DOI: 10.3389/fimmu.2020.00106
Access URL: https://doaj.org/article/87c4c20edc5c4f4ab1b9aa0b4309858a
Accession Number: edsdoj.87c4c20edc5c4f4ab1b9aa0b4309858a
Database: Directory of Open Access Journals
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  Data: Cervical Gene Delivery of the Antimicrobial Peptide, Human β-Defensin (HBD)-3, in a Mouse Model of Ascending Infection-Related Preterm Birth
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  Data: <searchLink fieldCode="AR" term="%22Natalie+Suff%22">Natalie Suff</searchLink><br /><searchLink fieldCode="AR" term="%22Rajvinder+Karda%22">Rajvinder Karda</searchLink><br /><searchLink fieldCode="AR" term="%22Juan+Antinao+Diaz%22">Juan Antinao Diaz</searchLink><br /><searchLink fieldCode="AR" term="%22Joanne+Ng%22">Joanne Ng</searchLink><br /><searchLink fieldCode="AR" term="%22Julien+Baruteau%22">Julien Baruteau</searchLink><br /><searchLink fieldCode="AR" term="%22Dany+Perocheau%22">Dany Perocheau</searchLink><br /><searchLink fieldCode="AR" term="%22Peter+W%2E+Taylor%22">Peter W. Taylor</searchLink><br /><searchLink fieldCode="AR" term="%22Dagmar+Alber%22">Dagmar Alber</searchLink><br /><searchLink fieldCode="AR" term="%22Suzanne+M%2E+K%2E+Buckley%22">Suzanne M. K. Buckley</searchLink><br /><searchLink fieldCode="AR" term="%22Mona+Bajaj-Elliott%22">Mona Bajaj-Elliott</searchLink><br /><searchLink fieldCode="AR" term="%22Simon+N%2E+Waddington%22">Simon N. Waddington</searchLink><br /><searchLink fieldCode="AR" term="%22Donald+Peebles%22">Donald Peebles</searchLink>
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  Data: Frontiers in Immunology, Vol 11 (2020)
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  Data: LCC:Immunologic diseases. Allergy
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  Data: <searchLink fieldCode="DE" term="%22cervix%22">cervix</searchLink><br /><searchLink fieldCode="DE" term="%22gene+therapy%22">gene therapy</searchLink><br /><searchLink fieldCode="DE" term="%22preterm+birth%22">preterm birth</searchLink><br /><searchLink fieldCode="DE" term="%22antimicrobial+peptides%22">antimicrobial peptides</searchLink><br /><searchLink fieldCode="DE" term="%22ascending+infection%22">ascending infection</searchLink><br /><searchLink fieldCode="DE" term="%22Immunologic+diseases%2E+Allergy%22">Immunologic diseases. Allergy</searchLink><br /><searchLink fieldCode="DE" term="%22RC581-607%22">RC581-607</searchLink>
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  Data: Approximately 40% of preterm births are preceded by microbial invasion of the intrauterine space; ascent from the vagina being the most common pathway. Within the cervical canal, antimicrobial peptides and proteins (AMPs) are important components of the cervical barrier which help to prevent ascending vaginal infection. We investigated whether expression of the AMP, human β-defensin-3 (HBD3), in the cervical mucosa of pregnant mice could prevent bacterial ascent from the vagina into the uterine cavity. An adeno-associated virus vector containing both the HBD3 gene and GFP transgene (AAV8 HBD3.GFP) or control AAV8 GFP, was administered intravaginally into E13.5 pregnant mice. Ascending infection was induced at E16.5 using bioluminescent Escherichia coli (E. coli K1 A192PP-lux2). Bioluminescence imaging showed bacterial ascent into the uterine cavity, inflammatory events that led to premature delivery and a reduction in pups born alive, compared with uninfected controls. Interestingly, a significant reduction in uterine bioluminescence in the AAV8 HBD3.GFP-treated mice was observed 24 h post-E. coli infection, compared to AAV8 GFP treated mice, signifying reduced bacterial ascent in AAV8 HBD3.GFP-treated mice. Furthermore, there was a significant increase in the number of living pups in AAV HBD3.GFP-treated mice. We propose that HBD3 may be a potential candidate for augmenting cervical innate immunity to prevent ascending infection-related preterm birth and its associated neonatal consequences.
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      – Text: English
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        Type: general
      – SubjectFull: gene therapy
        Type: general
      – SubjectFull: preterm birth
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      – SubjectFull: antimicrobial peptides
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      – SubjectFull: ascending infection
        Type: general
      – SubjectFull: Immunologic diseases. Allergy
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      – TitleFull: Cervical Gene Delivery of the Antimicrobial Peptide, Human β-Defensin (HBD)-3, in a Mouse Model of Ascending Infection-Related Preterm Birth
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