Journal Article

Impact of MyD88, Microbiota, and Location on Type 1 and Type 3 Innate Lymphoid Cells during Toxoplasma gondii Infection

Snyder, Lindsay M, Belmares-Ortega, Jessica, Doherty, Claire M, Denkers, Eric Y

2022

Overview

Toxoplasma gondii induces 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 with T. gondii. MyD88+/+ and MyD88−/− mice were orally inoculated with ME49 cysts, and small intestinal lamina propria ILC were assessed using flow cytometry. We observed T-bet+ ILC1, retinoic acid–related orphan receptor γt+ ILC3, and a population of T-bet+retinoic acid–related orphan receptor γt+ double-positive ILC. In MyD88−/− mice, IFN-γ–producing T-bet+ ILC1 frequencies were reduced compared with wild-type. Treatment of MyD88−/− mice with an antibiotic mixture to deplete microflora reduced IFN-γ+ ILC1 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.

• Subject: Animals / Immunity, Innate / Lymphocytes / Mice / Mice, Knockout / Microbiota / Myeloid Differentiation Factor 88 - genetics / Toxoplasmosis / Tretinoin