Survival of Helicobacter pylori From complement lysis by binding of GPI-anchored protectin (CD59).
OBJECTIVE
Although Helicobacter pylori is sensitive to complement lysis in vitro, chronic infection persists for years. We tested whether H. pylori acquires complement resistance by binding glycolipid-tailed inhibitors from the host.


METHODS
Gastric biopsy specimens from H. pylori-infected patients (n = 10) and noninfected controls (n = 6) were analyzed for complement deposition and expression of the complement regulators protectin (CD59) and DAF. Protectin binding and complement sensitivity analyses were performed with the NCTC strain 11637 (CagA(+)) and 2 clinical isolates 9:0 (CagA(+)) and 67:20 (CagA(-)).


RESULTS
In the noninfected mucosa, protectin was strongly expressed on the membranes of epithelial cells, but in the infected epithelia the expression was granular and more focused to the mucus. H. pylori bacteria in the gastric pits were often positive for protectin but negative for C5b-9. An opposite pattern was seen on the surface mucosa. In vitro analyses using (125)I-CD59 and bacteriolysis assays showed that protectin bound to H. pylori and protected CagA(+) strains against complement killing. In an enzyme-linked immunosorbent assay, the binding of CD59 correlated inversely with the appearance of the C5b-9 neoantigen.


CONCLUSIONS
Binding of protectin inhibits membrane attack complex assembly on H. pylori and may thereby contribute to their survival on the gastric mucosa.
Rautemaa
R
R
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland. riina.rautemaa@helsinki.fi
Rautelin
H
H
Puolakkainen
P
P
Kokkola
A
A
Kärkkäinen
P
P
Meri
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D018957:CD59 Antigens / Q000276:immunology / Q000378:metabolism*; D003167:Complement Activation / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005756:Gastritis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D017261:Glycosylphosphatidylinositols / Q000276:immunology / Q000378:metabolism; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000276:immunology; D013270:Stomach / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014774:Virulence / Q000276:immunology
D018957:CD59 Antigens; D017261:Glycosylphosphatidylinositols; D007457:Iodine Radioisotopes; D003165:Complement System Proteins