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Host Factors Affect Helicobacter pylori Outer Membrane Protein Expression during Experimental Infection
Mary E. Moore, Cathy M. Styer, Cara L. Cooke, Lori M. Hansen, and Jay V. Solnick
Host Factors Affect Helicobacter pylori Outer Membrane Protein Expression during Experimental Infection
Departments of Biochemistry and Molecular Biology, and Medicine and Medical Microbiology University of California, Davis
Abstract
INTRODUCTION: Helicobacter pylori from patients with peptic ulcer or gastric cancer frequently expresses the BabA adhesin, which binds to Lewisb (Leb) and related ABO blood group antigens on the gastric epithelium. We previously showed that expression of BabA and attachment to Leb are often lost in experimental animals. Here we utilized transgenic and knockout mice to understand the role of Leb expression and host immunity in selecting for loss of BabA expression. RESULTS: WT and Rag2-/- mice were challenged with H. pylori J166. Colonies recovered 1, 2, and 8 weeks later were examined for Leb attachment and babA ORF. Loss of attachment to Leb and the babA ORF occurred early after infection, and did not differ between WT and Rag2-/- mice, suggesting that adaptive immunity does not drive loss of BabA expression. To determine the role of innate immunity, we compared infection in WT mice to that in MyD88-/- mice. At 8 and 16 weeks of infection, the babA ORF was lost more often in WT than in MyD88-/- mice, suggesting that TLR-mediated immune responses may select for loss of BabA expression. Moreover, the babA ORF was rarely lost in strains recovered 8 weeks after challenge of C3H/HeJ mice, which are known to have a defective TLR4. To determine if availability of the Leb receptor affected BabA expression, we compared H. pylori recovered from male and female transgenic Leb mice to their WT littermates. In females, BabA expression was lost more commonly in WT than in Leb mice, but the opposite was observed in males. The difference in loss of BabA expression between genders was also observed when male and female Leb transgenic mice were infected with a more inflammatory clone of H. pylori SS1 engineered to express BabA.
CONCLUSIONS: TLR-mediated innate immune responses, and the presence of the Leb receptor, are host factors that alter H. pylori expression of BabA in mice. Similar processes probably occur in humans, though the relative selective pressures leading to disease phenotypes are likely different since about 70% of clinical isolates express BabA.
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