Involvement of Myeloid Dendritic Cells in the Development of Gastric Secondary Lymphoid Follicles inHelicobacter pylori-Infected Neonatally Thymectomized BALB/c Mice

Abstract

We previously described an animal model of Helicobacter pylori-induced follicular gastritis in neonatally thymectomized (nTx) mice. However, it is still not clear whether antigen-presenting dendritic cells (DCs) in the stomach have a role in the development of secondary follicles in H. pylori-infected nTx mice. We investigated the distribution of DC subsets using this model and examined their roles. To identify lymphoid and myeloid DCs, sections were stained with anti-CD11c (pan-DC marker) in combination with anti-CD8␣ (lymphoid DC marker) or anti-CD11b (myeloid DC marker) and were examined with a confocal microscope. Expression of macrophage inflammatory protein 3␣ (MIP-3␣), which chemoattracts immature DCs, was analyzed by realtime PCR and immunohistochemistry. Follicular dendritic cells (FDCs) were stained with anti-SKY28 antibodies. In noninfected nTx mice, a few myeloid and lymphoid DCs were observed in the bottom portion of the lamina propria, whereas in H. pylori-infected nTx mice, there was an increased influx of myeloid DCs throughout the lamina propria. FDC staining was also observed in the stomachs of members of the infected group. MIP-3␣ gene expression was upregulated in the infected nTx group, and the immunohistochemistry analysis revealed MIP-3␣-positive epithelial cells. These data suggest that H. pylori infection upregulates MIP-3␣ gene expression in gastric epithelial cells and induces an influx of myeloid DCs in the lamina propria of the gastric mucosa in nTx mice. Myeloid DCs and FDCs might contribute to the development of gastric secondary lymphoid follicles in H. pylori-infected nTx mice.Chronic Helicobacter pylori infection induces two distinct types of gastritis, chronic atrophic gastritis and nonatrophic gastritis (4). Nonatrophic gastritis is thought to be a predisposing factor for the development of mucosa-associated lymphoid tissue (MALT) lymphoma (8, 50). The organized structure of the secondary lymphoid tissues is believed to support proper regulation of activation and maturation of the antigen-responsive lymphoid cells (23,24). Although there is a substantial amount of data on the cellular elements that comprise the lymphoid and nonlymphoid components of the secondary lymphatic organs, little is known about the kinetics and roles of dendritic cells (DCs) that establish and maintain the proper organization of the secondary lymphoid tissues.DCs are immune regulatory cells that not only secrete chemokines and cytokines but also present antigens for T cells (39,42,43). In the intestine, DCs are constitutively present in the Peyer's patches, lamina propria, and mesenteric lymph nodes and have an essential role in the uptake of luminar bacterial antigens (37). Because normal gastric mucosa has no mucosaassociated lymphoid system, very little is known about the role of DCs in the mucosal immune system of the stomach, especially their role in H. pylori-induced chronic follicular gastritis.In previous studies (33, 46), it was demonstrated that H. pylori infection of BALB/c mice that were th...

Human Dendritic Cells Respond to Helicobacter pylori, Promoting NK Cell and Th1-Effector Responses In Vitro

“…It should be noted that the activated DCs were localized in the bottom portion of the lamina propria. Thus, the activated DCs might migrate to the regional lymph nodes where further interactions with immune cells can occur (12).…”

“…Indeed, follicular DCs have been detected in the H. pylori-inflamed gastric mucosa (11). H. pylori infection also up-regulated MIP-3-␣ gene expression in gastric epithelial cells and induced an influx of myeloid DCs in the lamina propria of the gastric mucosa in mice (12). However, the exact nature and function of these DCs has remained unclear because the cells are difficult to isolate and not abundant in the gastric mucosa.…”

Lineage relationships of human interleukin-22–producing CD56+ RORγt+ innate lymphoid cells and conventional natural killer cells

“…In addition, the chemokine receptors CCR6 and CXCR5 were mainly expressed on ILC22 cells, with only low-level expression on cNK cells ( Figure 3B). Because the ligands of these chemokines are involved in mucosal immunity and SLT generation, [37][38][39] ILC22 cell trafficking appears be different from cNK cells. 2 ) contain overlapping cell subsets including ILC22 cells and cNK progenitors that are discriminated by LFA-1 and CD7 expression.…”

Interplay between Helicobacter pylori and immune cells in immune pathogenesis of gastric inflammation and mucosal pathology

“…53,54 The production of CCL20 was upregulated in response to H. pylori in gastric epithelial cells when there was stimulation by the proinflammatory cytokines IL-1b and TNF-a. 15,[55][56][57] These results implicate that the interaction between CCL20 and CCR6 may play a role in recruiting CD45RO…”