Abstract Book - 26th ESPU Congress, Joint Meeting with ICCS + SPU + AAP/SOU + AAPU + SFU

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14:06 - 14:09
S1-13 (PP)
EXPRESSION AND ANTIMICROBIAL FUNCTION OF REG3GAMMA DURING
URINARY TRACT INFECTION
Christina CHING1, Ashley CARPENTER2, Birong LI3, John SPENCER3, Kirk MCHUGH4 and Brian BECKNELL 3
1) Nationwide Children's Hospital, Pediatric Urology, Columbus, USA - 2) Ohio State University, Biomedical Sciences,
Columbus, USA - 3) Research Institute at Nationwide Children's Hospital, Center for Clinical and Translational Research
and Microbial Pathogenesis, Columbus, USA - 4) Ohio State University, Anatomy, Columbus, USA
PURPOSE
Reg3g is an antimicrobial peptide (AMP) expressed by gastrointestinal, pulmonary and integumentary epithelium. Its
expression and antimicrobial function during urinary tract infections (UTI) is unknown. We hypothesized that Reg3g is
induced by uropathogens and required for UTI clearance.
MATERIAL AND METHODS
6 week old C67BL/6 wild type (Reg3g+/+) and Reg3gknock out (Reg3g-/-) female mice were inoculated transurethrally
with 108 colony forming units (CFU) uropathogenic Escherichia coli (UPEC), Enterococcus faecalis, or Staphylococcus
saprophyticus. Mice were sacrificed 24 hours post infection (hpi). We measured Reg3g mRNA by qRT-PCR, Reg3g
protein with immunoblotting and immunofluorescence, inflammatory cells using flow cytometry, and bladder bacterial
burden. We also tested bactericidal activity of recombinant Reg3g toward 105 CFU UPEC orS. saprophyticus.
RESULTS
Reg3gmRNA and protein expression was significantly induced in a time dependent manner inReg3g+/+bladders after
UPEC infection. RenalReg3gmRNA levels increased significantly in response to UPEC and Gram-positive
uropathogens. Reg3g protein localized to intermediate cells of infected bladder and renal urothelium and its expression
was mutually exclusive from that of Uroplakin 3a. There was no difference in inflammatory cell recruitment or recovery
of bacterial uropathogens inReg3g+/+ andReg3g-/- mice following infection. Recombinant Reg3g demonstrated dose-
dependent bactericidal activity towardS. saprophyticusbut did not kill UPEC.
CONCLUSIONS
Urothelial Reg3g expression increases in response to Gram-positive and UPEC infection, but Reg3g is dispensable for
bacterial clearance and leukocyte recruitment. We propose that Reg3g may synergize with other AMPs or serve a role in
urothelial regeneration/barrier function following bacterial infection.