RORγt+ Treg to Th17 ratios correlate with susceptibility to Giardia infection

Abstract

Infections with Giardia are among the most common causes of food and water-borne diarrheal disease worldwide. Here, we investigated Th17, Treg and IgA responses, and alterations in gut microbiota in two mouse lines with varying susceptibility to Giardia muris infection. Infected BALB/c mice shed significantly more cysts compared with C57BL/6 mice. Impaired control of infection in BALB/c mice was associated with lower Th17 activity and lower IgA levels compared with C57BL/6 mice. The limited metabolic activity, proliferation and cytokine production of Th17 cells in BALB/c mice was associated with higher proportions of intestinal Foxp3+RORγt+ regulatory T cells and BALB/c mice developed increased RORγt+ Treg:Th17 ratios in response to G. muris infection. Furthermore, G. muris colonization led to a significantly reduced evenness in the gut microbial communities of BALB/c mice. Our data indicate that differential susceptibility to Giardia infections may be related to RORγt+ Treg controlling Th17 activity and that changes in the microbiota composition upon Giardia infection partially depend on the host background.

Giardia spp. and the Gut Microbiota: Dangerous Liaisons

“…BALB/c mice infected with Giardia muris showed a more significant Treg response than C57BL/6 mice and shed more Giardia cysts. Interestingly, BALB/c mice showed larger populations of Clostridia than the C57BL/6 mice, further suggesting that presence of certain commensal species may drive specific immune responses ( Yordanova et al, 2019 ). However, in contrast to previous studies, although BALB/c mice showed increased SFB populations, they showed reduced Th17 responses ( Yordanova et al, 2019 ).…”

“…ATB = antibiotic treatment; * = phylum; + = class; $ = family # = genus; 1 = patients with severe malabsorption; 2 = taxa both enriched and decreased in separate studies. Microbiota dysbiosis in response to Giardia muris infections (i.e., Yordanova et al, 2019 ) is not represented in this figure.…”

Eosinophils are dispensable for the regulation of IgA and Th17 responses in Giardia muris infection

“…10-to 12-week old mice were infected and sacrificed at the indicated time points as previously described. 8 All animal experiments were performed in accordance with the National Animal Protection Guidelines and approved by the Berlin Ethics Committee for the Protection of Animals (G0113/15).…”

“…Surface and intracellular stainings were performed as previously described, 8 applying the antibodies listed in Table S1. Samples were analysed on a Canto II flow cytometer (BD Biosciences), and data were analysed using FlowJo software Version 10 (Tree star Inc.).…”

“…Tissue sampling, RNA isolation, cDNA preparation and quantitative real-time PCR (qRT-PCR) using 10 ng of cDNA and FastStart Universal SYBR Green Master Mix (Roche) were performed as described previously. 8 Efficiencies for each primer pair were determined by generating a standard curve, and mRNA expression was normalized to the housekeeping gene β-glucuronidase (GUSB).…”