Open AccessChronic Exposure toHelicobacter pyloriImpairs Dendritic Cell Function and Inhibits Th1 Development
Author(s) -
Peter Mitchell,
Conrad Germain,
Pier Luigi Fiori,
Wafa Khamri,
Graham R. Foster,
Subrata Ghosh,
Robert I. Lechler,
Kathleen B. Bamford,
Giovanna Lombardi
Publication year - 2007
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00228-06
Subject(s) - immune system , immunology , biology , helicobacter pylori , cd40 , interleukin 10 , population , downregulation and upregulation , dendritic cell , chronic infection , acquired immune system , t cell , cytotoxic t cell , medicine , in vitro , biochemistry , genetics , environmental health , gene
Helicobacter pylori causes chronic gastric infection that affects the majority of the world's population. Despite generating an inflammatory response, the immune system usually fails to clear the infection. Since dendritic cells (DCs) play a pivotal role in shaping the immune response, we investigated the effects ofH. pylori on DC function. We have demonstrated thatH. pylori increased the expression of activation markers on DCs while upregulating the inhibitory B7 family molecule, PD-L1. Functionally,H. pylori -treated DCs resulted in the production of interleukin-10 (IL-10) and IL-23 but not of alpha interferon (IFN-α). While very little or no IL-12 was produced toH. pylori alone, simultaneous ligation of CD40 on DCs induced IL-12 release. We also demonstrated that DCs treated withH. pylori -induced IFN-γ production by allogeneic naive T cells. However, stimulation of DCs withH. pylori for an extended period of time impaired their ability to produce cytokines after CD40 ligation and limited their ability to promote IFN-γ release, suggesting that the DCs had become exhausted by the prolonged stimulation. The effect of chronic infection withH. pylori on DC function was further investigated by focusing on DC development. Demonstrating that monocytes differentiated into DCs in the presence ofH. pylori exhibited an exhausted phenotype with an impaired ability to produce IL-12 and a downregulation of CD1a. Our results raise the possibility that in chronicH. pylori infection DCs become exhausted after prolonged antigen exposure leading to suboptimal Th1 development. This effect may contribute to persistence ofH. pylori infection.