title: IgA antibodies impair resistance against Helicobacter pylori infection: studies on immune evasion in IL-10-deficient mice.
abstract: We recently reported that Helicobacter pylori-specific Abs impair the development of gastritis and down-regulate resistance against H. pylori infection. In this study, we asked whether IgA Abs specifically can have an impact on H. pylori colonization and gastric inflammation. To obtain a sensitive model for the study of inflammation we crossed IgA- and IL-10-deficient mice. We found that IL-10(-/-)/IgA(-/-) mice were significantly less colonized than IL-10(-/-)/IgA(+/+) mice, which in turn were less colonized than wild-type (WT) mice. The IL-10(-/-)/IgA(-/-) mice exhibited a 1.2-log reduction in bacterial counts compared with that in IL-10(-/-)/IgA(+/+) mice, suggesting that IgA Abs rather promoted than prevented infection. The reduced colonization in IL-10(-/-)/IgA(-/-) mice was associated with the most severe gastritis observed, albeit all IL-10(-/-) mice demonstrated more severe gastric inflammation than wild-type mice. The gastritis score and the infiltration of CD4(+) T cells into the gastric mucosa were significantly higher in IL-10(-/-)/IgA(-/-) mice than in IL-10(-/-)/IgA(+/+) mice, arguing that IgA Abs counteracted inflammation. Moreover, following oral immunization, IL-10(-/-)/IgA(-/-) mice were significantly better protected against colonization than IL-10(-/-)/IgA(+/+) mice. However, the stronger protection was associated with more severe postimmunization gastritis and gastric infiltration of CD4(+) T cells. There was also a clear increase in complement receptor-expressing cells in IL-10(-/-)/IgA(-/-) mice, though C3b-fragment deposition in the gastric mucosa was comparable between the two. Finally, specific T cell responses to recall Ag demonstrated higher levels of IFN-gamma production in IL-10(-/-)/IgA(-/-) as compared with IL-10(-/-)/IgA(+/+) mice. Thus, it appears that IgA and IL-10 help H. pylori bacteria evade host resistance against infection.
authors.affiliation: Department of Clinical Immunology, Göteborg University, Göteborg, Sweden. ali.akhiani@microbio.gu.se
authors.forename: Ali A
authors.initials: AA
authors.lastname: Akhiani
authors.forename: Anneli
authors.initials: A
authors.lastname: Stensson
authors.forename: Karin
authors.initials: K
authors.lastname: Schön
authors.forename: Nils Y
authors.initials: NY
authors.lastname: Lycke
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000235:genetics / Q000502:physiology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D016481:Helicobacter Infections / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity*; D007113:Immunity, Innate / Q000235:genetics; D007070:Immunoglobulin A / Q000235:genetics / Q000502:physiology*; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma