Background Natural killer (NK) cells contribute to the innate inflammatory response mounted against viral infections and tumors; however, the role of NK cells in the response to bacterial infection has not been elucidated. To investigate this, we infected both mice deficient in NK cells and wild-type mice with Helicobacter felis, a gram-negative bacterium that colonizes the gastrointestinal tract and initiates mucosal changes that lead to gastritis and, less frequently, gastric adenocarcinoma. We hypothesized that mice deficient in NK cells would mount a lesser inflammatory response to H. felis.
Methods C57BL/6 mice and NK cell-deficient transgenic (NKD) mice on a C57BL/6 background were infected with H. felis. The mice were sacrificed at 2-week and 40-week time points. The stomachs were extracted and cut in half. One half was snap frozen for RNA isolation, and the other half was fixed in a 2% PFA/sucrose solution for histology. RNA was isolated using the Trizol® method (Invitrogen, Inc) and cDNA was synthesized using the First Stand Transcriptor Kit® (Roche, Inc). Real-time PCR was performed to measure the expression of H,K-ATPase, IL-10, IL-17, IL-6, IFN-γ, KC, LIX, and MIP-2 (murine IL-8) using Assay on Demand® (Applied Biosystems). The crossing threshold of each cytokine was normalized to 18S ribosomal RNA expression. Fold change in expression was compared to strain-matched mock-infected animals. The degree of H. felis colonization was determined by immunohistochemistry.
Results NKD mice exhibited decreased clearance of the bacteria and decreased pathology at both 2 weeks and 40 weeks postinfection when compared with their C57BL/6 counterparts. NKD mice also expressed significantly lower levels of mRNA transcripts for inflammatory cytokines than did the C57BL/6 mice. Cytokine levels by ELISA confirmed the RT-PCR results.
Conclusions In the murine model, NK cells play a role in the clearance of H. felis and the inflammation associated with H. felis infection.
Implications Mice lacking NK cells exhibit a weaker and delayed immune response to H. felis infection. Although NK cells are typically thought to act as part of the innate immune system, further studies should be performed to investigate whether NK cells only act directly against the pathogen or if they act indirectly via the activation of the adaptive immune system.
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