Abstract
Intestinal infection with the intracellular parasite Toxoplasma gondii results in the translocation of commensal bacteria to peripheral organs and the development of a T cell response specific to the microbiota. In naïve mice, the recently described RORγt+ group 3 innate lymphoid cell (ILC) population plays a critical role in promoting intestinal barrier function and limiting responses to gut-resident commensal bacteria. Given this role for group 3 ILCs, studies were performed to evaluate whether these cells might influence the immune response to mucosal infection with T. gondii. Phenotypic characterization of RORγt+ ILCs in T. gondii infected mice revealed that this population decreased following challenge but the population that remained expressed costimulatory molecules and IL-22. One factor that influences the maintenance of RORγt+ ILCs is the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, and Ahr-/- mice have a marked defect in the lamina propria group 3 ILC population. When Ahr-/- mice were challenged with T. gondii, they lost more weight than wild type controls. This disease course in Ahr-/- animals was associated with increased T cell responses to Toxoplasma antigen and crude commensal antigen preparations. Together, these data suggest that group 3 ILCs have a role in limiting T cell activation during intestinal infection.
Highlights
The ability of cells of the immune system to sense and react to environmental stimuli plays a crucial role in the maintenance of steady state conditions and in the effective control of infection while limiting immune-mediated damage to the host
Oral infection with T. gondii led to a decrease in the frequency and number of RORγt+ innate lymphoid cell (ILC) in the lamina propria (Fig 1C), which was associated with decreased expression of RORγt by these cells in infected mice and increased expression of Ki67 (Fig 1D)
These results show that challenge with T. gondii led to marked changes in the group 3 ILC population, and suggest that despite the overall reduction in this population, there was an increased frequency of these cells undergoing proliferation
Summary
The ability of cells of the immune system to sense and react to environmental stimuli plays a crucial role in the maintenance of steady state conditions and in the effective control of infection while limiting immune-mediated damage to the host. AHR ligands derived from plants can be obtained through the diet [3], which makes the intestines a major site of exposure to AHR agonists Signaling through this transcription factor has multiple effects on intestinal immune responses. AHR activity in the intestine is required for the development of isolated lymphoid follicles and cryptopatches, and contributes to the maintenance of intraepithelial lymphocytes and group 3 innate lymphoid cells (ILCs) [4,5,6,7] This RORγt+ ILC population has a critical role in the regulation of intestinal barrier function in naïve mice and IL-22 expression by these cells limits the dissemination of the microbiota to distal sites [8]. Group 3 ILCs are able to present antigen but because they typically lack the expression of costimulatory molecules, they are thought to promote T cell tolerance to commensal bacteria [9]
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