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

F Hu, G Ding, Z Zhang, LA Gatto, S Hawgood… - Innate …, 2016 - journals.sagepub.com
F Hu, G Ding, Z Zhang, LA Gatto, S Hawgood, FR Poulain, RN Cooney, G Wang
Innate immunity, 2016journals.sagepub.com
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 …
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.
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