RT Journal Article
SR Electronic
T1 Cervical gene delivery of the antimicrobial peptide, Human β-defensin (HBD)-3, in a mouse model of ascending infection-related preterm birth
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 643171
DO 10.1101/643171
A1 Natalie Suff
A1 Rajvinder Karda
A1 Juan Antinao Diaz
A1 Joanne Ng
A1 Julien Baruteau
A1 Dany Perocheau
A1 Peter W. Taylor
A1 Dagmar Alber
A1 Suzanne M.K. Buckley
A1 Mona Bajaj-Elliott
A1 Simon N. Waddington
A1 Donald Peebles
YR 2019
UL http://biorxiv.org/content/early/2019/05/20/643171.abstract
AB Approximately 40% of preterm births are preceded by microbial invasion of the intrauterine space: ascent from the vagina is the most common pathway. Within the cervical canal, antimicrobial peptides and proteins (AMPs) help to constitute a barrier which prevents ascending infection. We investigated whether expression of the AMP, human β-defensin-3 (HBD3), in the cervical mucosa prevented bacterial ascent from the vagina into the uterine cavity of pregnant mice. 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 E.coli (E.coli K1 A192PP-lux2). Bioluminescence imaging showed bacterial ascent into the uterine cavity, cellular events that led to premature delivery and a reduction in pups born alive, compared with uninfected controls. In addition, a significant reduction in uterine bioluminescence in the AAV8 HBD3.GFP-treated mice was observed 24 hours post-E.coli infection, compared to AAV8 GFP treated mice, signifying reduced bacterial ascent in AAV8 HBD3.GFP-treated mice. There was also an increase in the number of living pups in AAV HBD3.GFP-treated mice. We propose that HBD3 may be considered a possible candidate for augmenting cervical innate immunity to prevent ascending infection-related preterm birth.