Contribution of Secretory Antibodies to Intestinal Mucosal Immunity against Helicobacter pylori

Abstract

dThe natural immune response to Helicobacter pylori neither clears infection nor prevents reinfection. However, the ability of secretory antibodies to influence the course of H. pylori infection has not been determined. We compared the natural progression of H. pylori infection in wild-type C57BL/6 mice with that in mice lacking the polymeric immunoglobulin receptor (pIgR) that is essential for the secretion of polymeric antibody across mucosal surfaces. H. pylori SS1-infected wild-type and pIgR knockout (KO) mice were sampled longitudinally for gastrointestinal bacterial load, antibody response, and histological changes. The gastric bacterial loads of wild-type and pIgR KO mice remained constant and comparable at up to 3 months postinfection (mpi) despite SS1-reactive secretory IgA in the intestinal contents of wild-type mice at that time. Conversely, abundant duodenal colonization of pIgR KO animals contrasted with the near-total eradication of H. pylori from the intestine of wild-type animals by 3 mpi. H. pylori was cultured only from the duodenum of those animals in which colonization in the distal gastric antrum was of sufficient density for immunohistological detection. By 6 mpi, the gastric load of H. pylori in wild-type mice was significantly lower than in pIgR KO animals. While there was no corresponding difference between the two mouse strains in gastric pathology results at 6 mpi, reductions in gastric bacterial load correlated with increased gastric inflammation together with an intestinal secretory antibody response in wild-type mice. Together, these results suggest that naturally produced secretory antibodies can modulate the progress of H. pylori infection, particularly in the duodenum.

Helicobacter pylori and Nonmalignant Diseases

“…Finally, secretory antibodies can modulate the progress of H. pylori infection, particularly in the duodenum, as shown by Gorrell et al. : Knockout mice for polymeric immunoglobulin receptors had a very intense colonization of the duodenum .…”

“…Even though a clear relationship could not be found, basic research demonstrated that H. pylori can use its pathogenic action against colonic cells, when they produce a gastric mucin (MUC5AC) [38]. Finally, secretory antibodies can modulate the progress of H. pylori infection, particularly in the duodenum, as shown by Gorrell et al: Knockout mice for polymeric immunoglobulin receptors had a very intense colonization of the duodenum [39].…”

Helicobacter pylori Infection of the Gastric Mucosa

“…A systematic analysis of studies on the role of breast-feeding in H. pylori infection has shown that breast-feeding can indeed protect against acquisition of new H. pylori infection, particularly in children in low-and middle-income countries (Chak et al, 2009). Further support for a protective role of SIgA antibodies came from a study showing that, whereas H. pylori infection in WT mice was spontaneously eradicated from the duodenum after three months, knockout mice lacking polymeric Ig receptor were abundantly colonized with H. pylori in the duodenum (Gorrell et al, 2013). Thus, H. pylori-specific SIgA antibodies may play a role in preventing acquisition of H. pylori infection by immune exclusion.…”

Features of the human immune response to Helicobacter pylori infection

“…В некоторых исследованиях показано, что IgA содержится в желудочном соке большинства H. рylori инфицированных носителей, а в слюне этих пациентов выявлены sIgA. Предполагают, что наличие IgA в высоких титрах может говорить о повреждении эпителия слизистой желудка [26,27].…”