Human Alpha Defensin 5 Expression in the Human Kidney and Urinary Tract

Abstract

BackgroundThe mechanisms that maintain sterility in the urinary tract are incompletely understood. Recent studies have implicated the importance of antimicrobial peptides (AMP) in protecting the urinary tract from infection. Here, we characterize the expression and relevance of the AMP human alpha-defensin 5 (HD5) in the human kidney and urinary tract in normal and infected subjects.Methodology/Principal FindingsUsing RNA isolated from human kidney, ureter, and bladder tissue, we performed quantitative real-time PCR to show that DEFA5, the gene encoding HD5, is constitutively expressed throughout the urinary tract. With pyelonephritis, DEFA5 expression significantly increased in the kidney. Using immunoblot analysis, HD5 production also increased with pyelonephritis. Immunostaining localized HD5 to the urothelium of the bladder and ureter. In the kidney, HD5 was primarily produced in the distal nephron and collecting tubules. Using immunoblot and ELISA assays, HD5 was not routinely detected in non-infected human urine samples while mean urinary HD5 production increased with E.coli urinary tract infection.Conclusions/Significance DEFA5 is expressed throughout the urinary tract in non-infected subjects. Specifically, HD5 is expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney. With infection, HD5 expression increases in the kidney and levels become detectable in the urine. To our knowledge, our findings represent the first to quantitate HD5 expression and production in the human kidney. Moreover, this is the first report to detect the presence of HD5 in infected urine samples. Our results suggest that HD5 may have an important role in maintaining urinary tract sterility.

LRRC19 expressed in the kidney induces TRAF2/6-mediated signals to prevent infection by uropathogenic bacteria

“…Moreover, LRRC19 expressed in kidney tubular cells not only modulated the expression of inflammatory cytokines but also antimicrobial peptides and proteins, such as a-defensin-5, Reg3g and cathelicidin. Importantly, we found that LRRC19-deficient kidney tubular cells also have a reduced ability to kill UPEC, consistent with the fact that the antimicrobial substances have antibacterial activity against common uropathogenic Grampositive bacteria and Gram-negative bacteria 6,[8][9][10] . Thus, LRRC19 in kidney tubule cells is involved not only in attracting inflammatory cells but also in kidney-mediated killing of uropathogenic bacteria.…”

“…Consistent with other data [6][7][8][9] , kidney also expressed different kinds of bactericidal substance ( Supplementary Fig. 6a).…”

“…7), a-defensin-5 (ref. 8) and cathelicidins 9 . In addition, C-type lectins such as Reg3 are also found in the epithelial cells 10 .…”

Molecular Defense Mechanisms during Urinary Tract Infection

“…HD5 showed bactericidal activity at minimal concentration of 0.3 M [58]. However, it is reported that HD5 does not reach sufficient concentrations to kill bacteria in the urinary tract [59]. The role of HD5 in innate immunity of urinary tract is not fully known.…”

Carbonic anhydrase 2 deficiency leads to increased pyelonephritis susceptibility

“…Renal ribonuclease 7 expression is limited to ICs, constitutively expressed at baseline, upregulated in response to infection, and secreted into the urine (42,43). ICs have been demonstrated to express other innate immune proteins, including neutrophil gelatinase-associated lipocalin, also known as lipocalin 2 (gene: Lcn2; protein: Ngal), IL-18 (gene: Il18), and human ␣-defensin 5 (15,28,41). Additionally, uropathogenic Escherichia coli (UPEC) preferentially adhere to the luminal surface of medullary ICs (10).…”