IgA antibodies impair resistance against Helicobacter pylori infection: studies on immune evasion in IL-10-deficient mice.

• 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.

Keyword

Animals

Antibodies

Bacterial

genetics

physiology

Bacterial Vaccines

administration & dosage

immunology

Gastric Mucosa

immunology

microbiology

pathology

Gastritis

genetics

immunology

pathology

prevention & control

Helicobacter Infections

genetics

immunology

pathology

prevention & control

Helicobacter pylori

immunology

pathogenicity

Immunity

Natural

genetics

Immunoglobulin A

genetics

physiology

Immunoglobulin M

biosynthesis

blood

physiology

Interferon Type II

biosynthesis

Interleukin-10

deficiency

genetics

physiology

Interleukin-12

biosynthesis

Mice

Mice

Inbred C57BL

Mice

Knockout

Th1 Cells

immunology

metabolism

microbiology

Up-Regulation

genetics

immunology

Publication and Content Type

ref (subject category)

art (subject category)