A novel IL-17-dependent mechanism of cross protection: Respiratory infection with mycoplasma protects against a secondary listeria infection

Abstract

Immune responses to pathogens occur within the context of current and previous infections. Cross protection refers to the phenomena where infection with a particular pathogen provides enhanced resistance to a subsequent unrelated pathogen in an antigen‐independent manner. Proposed mechanisms of antigen‐independent cross protection have involved the secretion of IFN‐γ, which activates macrophages, thus providing enhanced innate immunity against the secondary viral or bacterial pathogen. Here we provide evidence that a primary infection with the chronic respiratory pathogen, Mycoplasma pulmonis , provides a novel form of cross protection against a secondary infection with Listeria monocytogenes that is not mediated by IFN‐γ, but instead relies upon IL‐17 and mobilization of neutrophils. Mice infected with M. pulmonis have enhanced clearance of L. monocytogenes from the spleen and liver, which is associated with increased numbers of Gr‐1⁺CD11b⁺ cells and higher levels of IL‐17. This enhanced clearance of L. monocytogenes was absent in mice depleted of Gr‐1⁺ cells or in mice deficient in the IL‐17 receptor. Additionally, both the IL‐17 receptor and neutrophils were essential for optimal clearance of M. pulmonis . Thus, a natural component of the immune response directed against M. pulmonis was able to enhance clearance of L. monocytogenes .