Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli.
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.
Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, USA Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.
Fengqi
F
Hu
Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.
Guohua
G
Ding
Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, USA.
Zhiyong
Z
Zhang
Department of Biological Sciences, SUNY Cortland, Cortland, NY, USA.
Louis A
LA
Gatto
Department of Pediatrics and the Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
Samuel
S
Hawgood
Division of Neonatology, Department of Pediatrics, Children's Hospital, University of California Davis Medical Center, Davis, CA, USA.
Francis R
FR
Poulain
Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, USA.
Robert N
RN
Cooney
Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, USA wangg@upstate.edu ghxding@gmail.com.
Guirong
G
Wang
D000818:Animals; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism*; D014551:Urinary Tract / Q000276:immunology* / Q000382:microbiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D020381:Interleukin-17; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D048051:p38 Mitogen-Activated Protein Kinases
Innate immunity; surfactant protein A; surfactant protein D; urinary tract infection; uropathogenic Escherichia coli