Supplementary Material for: Helicobacter pylori Inhibits Dendritic Cell Maturation via Interleukin-10-Mediated Activation of the Signal Transducer and Activator of Transcription 3 Pathway

Helicobacter pylori infects the human gastric mucosa causing a
chronic infection that is the primary risk factor for gastric cancer
development. Recent studies demonstrate that H. pylori promotes
tolerogenic dendritic cell (DC) development indicating that this
bacterium evades the host immune response. However, the signaling
pathways involved in modulating DC activation during infection remain
unclear. Here, we report that H. pylori infection activated the
signal transducer and activator of transcription 3 (STAT3) pathway in
murine bone marrow-derived DCs (BMDCs) and splenic DCs isolated ex vivo.
Isogenic cagA-, cagE-, vacA- and urease-mutants exhibited levels of phosphoSTAT3 that were comparable to in the wild-type (WT) parent strain. H. pylori-infected
BMDCs produced increased immunosuppressive IL-10, which activated STAT3
in an autocrine/paracrine fashion. Neutralization of IL-10 prevented H. pylori-mediated STAT3 activation in both BMDCs and splenic DCs. In addition, anti-IL-10 treatment of infected H. pylori-BMDCs
was associated with increased CD86 and MHC II expression and enhanced
proinflammatory IL-1β cytokine secretion. Finally, increased CD86 and
MHC II expression was detected in H. pylori-infected STAT3 knockout DCs when compared to WT controls. Together, these results demonstrate that H. pylori
infection induces IL-10 secretion in DCs, which activates STAT3,
thereby modulating DC maturation and reducing IL-1β secretion. These
findings identify a host molecular mechanism by which H. pylori can manipulate the innate immune response to potentially favor chronic infection and promote carcinogenesis.