Helicobacter infection in the surfactant protein D-deficient mouse.
BACKGROUND
Surfactant protein D (SP-D), a component of innate immunity, is expressed in the gastric mucosa and is up-regulated in the presence of Helicobacter infection. SP-D binds to Helicobacter in vitro, suggesting the involvement of SP-D in Helicobacter-induced immune responses. The aim of this study was to determine the role of SP-D in gastric epithelial defense in vivo.


METHODS
Specific pathogen-free SP-D-deficient mice (SP-D(-/-)) and C57BL/6 wild-type controls were challenged by gavage with different doses of Helicobacter felis, a mouse-adapted Helicobacter strain. Mice were assessed for colonization rates and density of infection. Inflammatory responses were measured by neutrophil counting and T-cell responses by proliferation assays on spleen cells stimulated with H. felis sonicate. The in vitro effect of SP-D on Helicobacter uptake by monocyte-derived dendritic cells was assessed by confocal microscopy and FACS analyses.


RESULTS
SP-D(-/-) mice were more susceptible to low-dose infectious challenge than C57BL/6 controls (p = .02). The density of colonization was higher in the SP-D(-/-) infected mice. Neutrophil infiltrates were lower in the SP-D(-/-) mice, particularly in the acid-secreting regions of the stomach. T-cell proliferative responses to Helicobacter antigen were reduced in SP-D(-/-) mice (p = .001) after 12 weeks infection. In vitro uptake of Helicobacter by dendritic cells was significantly enhanced in the presence of SP-D (p = .001).


CONCLUSIONS
In the absence of SP-D, Helicobacter uptake by dendritic cells is impaired. This provides an explanation for the diminished inflammation and immune responses in the SP-D(-/-) mice.
Khamri
Wafa
W
Faculty of Medicine, Imperial College, St Mary's Campus, London, UK. wafa.khamri@kcl.ac.uk
Worku
Mulugeta L
ML
Anderson
Amy E
AE
Walker
Marjorie M
MM
Hawgood
Samuel
S
Reid
Kenneth B M
KB
Clark
Howard W
HW
Thursz
Mark R
MR
D000371:Agglutination; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000382:microbiology; D005260:Female; D005756:Gastritis / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D044922:Helicobacter felis / Q000276:immunology / Q000472:pathogenicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000473:pathology
D037663:Pulmonary Surfactant-Associated Protein D