Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli

Innate Immun. 2016 Jan;22(1):9-20. doi: 10.1177/1753425915609973. Epub 2015 Oct 28.

Abstract

To investigate the effects of surfactant proteins A and D (SP-A and SP-D, respectively) in urinary tract infection (UTI), SP-A and SP-D double knockout (SP-A/D KO) and wild type (WT) C57BL/6 female mice were infected with uropathogenic Escherichia coli by intravesical inoculation. Compared with WT mice SP-A/D KO mice showed increased susceptibility to UTI, as evidenced by higher bacterial CFU, more infiltrating neutrophils and severe pathological changes. Keratinocyte-derived chemokine increased in the kidney of WT mice but not in SP-A/D KO mice 24 h post-infection. Compared with control, the level of IL-17 was elevated in the kidney of infected WT and SP-A/D KO mice and the level of IL-17 was higher in the infected SP-A/D KO mice than in infected WT mice 24 and 48 h post-infection. The basal level of p38 MAPK phosphorylation in SP-A/D KO mice was higher than in WT mice. The phosphorylated p38 level was elevated in the kidney of WT mice post infection but not in SP-A/D KO mice. Furthermore, in vitro growth of uropathogenic E. coli was inhibited by SP-A and SP-D. We conclude that SP-A and SP-D function as mediators of innate immunity by inhibiting bacterial growth and modulating renal inflammation in part by regulating p38 MAPK-related pathway in murine UTI.

Keywords: Innate immunity; surfactant protein A; surfactant protein D; urinary tract infection; uropathogenic Escherichia coli.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Escherichia coli / immunology*
  • Escherichia coli Infections / immunology*
  • Female
  • Humans
  • Immunity, Innate
  • Interleukin-17 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphorylation
  • Pulmonary Surfactant-Associated Protein A / genetics
  • Pulmonary Surfactant-Associated Protein A / metabolism*
  • Pulmonary Surfactant-Associated Protein D / genetics
  • Pulmonary Surfactant-Associated Protein D / metabolism*
  • Urinary Tract / immunology*
  • Urinary Tract / microbiology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Interleukin-17
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Protein D
  • p38 Mitogen-Activated Protein Kinases