CD1d KO Research Articles

CD1d-independent regulation of NKT cell migration and cytokine production upon Listeria monocytogenes infection

Natural killer T (NKT) cells are a unique T-cell population that is positively selected by CD1d-expressing cells. In this study, we examined the kinetics of conventional CD4 +TCRβ + and CD4 −TCRβ + cells along with various NKT cell populations from WT and CD1d KO mice after oral Listeria monocytogenes (Lm) infection at different time points in tissue compartments. We found that CD4 +TCRβ + cells expressing NK1.1 + (NKT) were constitutively expressed in the lung of both strains of mice, but disappeared after infection. In contrast, CD4 −TCRβ + NK1.1 + cells migrated to the spleen. Here, we demonstrated that endogenous IL-12 was predominantly expressed in the spleen of CD1d KO mice 2 days after infection, whereas IL-4 was predominantly expressed in the liver of WT mice. Higher levels of IFN-γ were expressed in MLN of CD1d KO but not in WT mice on day 5. Thus, tissue-specific ligands orchestrate the localization and activation of NKT cells to control immune response to Listeria, which may explain the difference in disease susceptibility.

The role of CD1d in the immune response against Listeria infection

To address the role of CD1d in mucosal immune regulation in bacterial infection, we infected CD1d KO mice with Listeria monocytogenes (Lm). A higher systemic bacterial burden associated with inflammatory lymphocytic infiltrations within the intestine was found in CD1d KO compared with wild type (WT) mice. Lm induced strong IFN-γ mRNA expression in the liver of WT and the intestine of CD1d KO mice, thus demonstrating the dual, opposing immune activities of IFN-γ in Lm infection that is dependent on CD1d and/or NKT cells. Analysis of hepatic T cell population demonstrated a reduction of NK1.1 +TCRβ + cells in both mice, followed by recovery only in WT mice. Last, the proportion of α4β1 integrin on lung lymphocytes from CD1d KO was dramatically increased compared with WT mice. Thus, the absence of CD1d resulted in increased susceptibility towards Listeria infection, induced changes in NKT cells, and increased trafficking of α4β1 molecule to inflamed lung.