| Popis: |
iToxoplasma gondii/iinduces strong IFN-γ-based immunity. Innate lymphoid cells (ILC), in particular ILC1, are an important innate source of this protective cytokine during infection. Our objective was to determine how MyD88-dependent signaling influences ILC function during peroral compared with i.p. infection withiT. gondii. MyD88/isup+/+/supandiMyD88/isup-/-/supmice were orally inoculated with ME49 cysts, and small intestinal lamina propria ILC were assessed using flow cytometry. We observed T-betsup+/supILC1, retinoic acid-related orphan receptor γtsup+/supILC3, and a population of T-betsup+/supretinoic acid-related orphan receptor γtsup+/supdouble-positive ILC. IniMyD88/isup-/-/supmice, IFN-γ-producing T-betsup+/supILC1 frequencies were reduced compared with wild-type. Treatment ofiMyD88/isup-/-/supmice with an antibiotic mixture to deplete microflora reduced IFN-γsup+/supILC1 frequencies. To examine ILC responses outside of the mucosal immune system, peritoneal exudate cells were collected from wild-type and knockout mice after i.p. inoculation with ME49 cysts. In this compartment, ILC were highly polarized to the ILC1 subset that increased significantly and became highly positive for IFN-γ over the course of infection. Increased ILC1 was associated with expression of the Ki67 cell proliferation marker, and the response was driven by IL-12p40. In the absence of MyD88, IFN-γ expression by ILC1 was not maintained, but proliferation remained normal. Collectively, these data reveal new aspects of ILC function that are influenced by location of infection and shaped further by MyD88-dependent signaling. |
