IL-4 secretion by CD4+ NK1+ T cells induces monocyte chemoattractant protein-1 in early listeriosis.

IL-4 is a major promotor of Th2 differentiation and an antagonist of IFN-gamma production. Although experimental listeriosis is characterized by a Th1 response, IL-4-producing cells were detected in spleens of mice promptly after Listeria monocytogenes infection. We identified this early IL-4 as inducer of the chemokine, monocyte chemoattractant protein-1 (MCP-1), which mainly attracts monocytes/macrophages, but not neutrophils. MCP-1-secreting cells were demonstrable in spleens of mice infected with L. monocytogenes, and IL-4 neutralization with anti-IL-4 mAb 11B11 markedly diminished frequencies of MCP-1-producing cells. Cell depletion experiments and studies with gene disruption mutant mice lacking distinct T cell subsets and surface MHC molecules point to CD4+ NK1+ T cells as a cellular source of early IL-4. Since monocyte infiltration to infective foci contributes to early control of listeriosis, our results suggest that IL-4-producing CD4+ NK1+ T cells participate in the innate immune response against L. monocytogenes through MCP-1 induction.