APRIL-producing eosinophils are involved in gastric MALT lymphomagenesis induced by Helicobacter sp infection

Abstract

The roles of the inflammatory response and production of a proliferation-inducing ligand (APRIL) cytokine in gastric mucosa-associated lymphoid tissue (MALT) lymphomagenesis induced by Helicobacter species infection are not clearly understood. We characterized the gastric mucosal inflammatory response associated with gastric MALT lymphoma (GML) and identified APRIL-producing cells in two model systems: an APRIL transgenic mouse model of GML induced by Helicobacter infection (Tg-hAPRIL) and human gastric biopsy samples from Helicobacter pylori-infected GML patients. In the mouse model, polarization of T helper 1 (tbet), T helper 2 (gata3), and regulatory T cell (foxp3) responses was evaluated by quantitative PCR. In humans, a significant increase in april gene expression was observed in GML compared to gastritis. APRIL-producing cells were eosinophilic polynuclear cells located within lymphoid infiltrates, and tumoral B lymphocytes were targeted by APRIL. Together, the results of this study demonstrate that the Treg-balanced inflammatory environment is important for gastric lymphomagenesis induced by Helicobacter species, and suggest the pro-tumorigenic potential of APRIL-producing eosinophils.

Two rare cases of bronchus‐associated lymphoid tissue lymphoma successfully treated with rituximab‐bendamustine

“… 10 This link is most clearly established for Helicobacter pylori and gastric MALT lymphoma. 32 , 33 , 34 The importance of this stimulation in vivo has been clearly demonstrated by the induction of remissions in gastric MALT lymphomas with antibiotic treatment to eradicate Helicobacter pylori. 35 , 36 A role for antigenic stimulation by Chlamydia psittaci and Borrelia burgdorferi has been proposed for some cases of ocular adnexal and cutaneous MALT lymphomas, respectively.…”

“… 34 , 39 , 40 The eradication of Helicobacter pylori associated with gastric or Chlamydia psittaci causing ocular adnexa MALT lymphoma by antibiotic therapy led to protracted remissions. 10 , 32 , 34 , 39 , 41 Thus, successful eradication or removal of suspected trigger factors, for example, smoking, should be of utmost priority.…”

Bacterial Infection and Non-Hodgkin B-Cell Lymphoma: Interactions between Pathogen, Host and the Tumor Environment

“…Chronic H. pylori infection induces the secretion of pro-inflammatory cytokines by macrophages and dendritic cells, such as interleukin-1 beta (IL-1β), TNF-α, IL-8 and IL-6, and allows differentiation of Th1 and Th17 cells, which are involved in establishing persistent inflammation [ 38 ]. In gastric MALT-lymphoma, H. pylori -induced antigenic stimulation results in the formation of T-cell infiltrates that invade and destroy gastric glands [ 39 ]. These reactive Th1 CD4 + lymphocytes produce high levels of IFN-γ, and facilitate the proliferation of neoplastic B cells through CD40L-CD40 co-stimulation, and the secretion of Th2 cytokines including IL-4 [ 40 ].…”

“…Recent findings indicated that a proliferation-inducing ligand (APRIL) expressed by neutrophils, eosinophils and tumor-infiltrating macrophages seems to be important for gastric lymphogenesis induced by H. pylori [ 42 ]. Recently, Blosse et al characterized the inflammatory response associated with gastric MALT lymphoma in the stomach of transgenic C57BL/6 mice, and additionally found APRIL-producing eosinophilic polynuclear cells in the lymphoid infiltrates of patients with gastric MALT lymphoma [ 39 ]. The authors have demonstrated that the T reg -balanced inflammatory environment is an important contributor to gastric lymphogenesis [ 39 ].…”

“…Recently, Blosse et al characterized the inflammatory response associated with gastric MALT lymphoma in the stomach of transgenic C57BL/6 mice, and additionally found APRIL-producing eosinophilic polynuclear cells in the lymphoid infiltrates of patients with gastric MALT lymphoma [ 39 ]. The authors have demonstrated that the T reg -balanced inflammatory environment is an important contributor to gastric lymphogenesis [ 39 ]. In recent years, studies have examined the role of the PD-1 pathway in the context of H. pylori colonization, and T-cell dysfunction and PD-1 expression have been observed in these patients [ 43 ].…”