Interleukin 10 controls the balance between tolerance, pathogen elimination and immunopathology in birds

Reviewer #1 (Public review):

Summary:

In this study, Meunier et al. investigated the functional role of IL-10 in avian mucosal immunity. While the anti-inflammatory role of IL-10 is well established in mammals, and several confirmatory knockout models are available in mice, IL-10's role in avian mucosal immunity is so far correlative. In this study, the authors generated two different models of IL-10 ablation in Chickens. A whole body knock-out model and an enhancer KO model leading to reduced IL10 expression. The authors first performed in vitro LPS stimulation-based experiments, and then in vivo two different infection models employing C. jejuni and E. tenella, to demonstrate that complete ablation of IL10 leads to enhanced inflammation-related pathology and gene expression, and enhanced pathogen clearance. At a steady-state level, however, IL-10 ablation did not lead to spontaneous colitis.

Strengths:

Overall, the study is well executed and establishes an anti-inflammatory role of IL-10 in birds. While the results are expected and not surprising, this appears to be the first report to conclusively demonstrate IL-10's anti-inflammatory role upon its genetic ablation in the avian model. Provided this information is applicable in combating pathogen infection in livestock species in sustainable industries like poultry, the study will be of interest to the field.

Weaknesses:

The study is primarily a confirmation of the already established anti-inflammatory role of IL-10.

Reviewer #2 (Public review):

Summary:

The authors were to investigate the functional role of IL10 on mucosal immunity in chickens. CRISPR technology was employed to generate IL10 knock-out chickens in both exon and putative enhancer regions. IL10 expressions were either abolished (knockout in exon) or reduced (enhancer knock-out). IL-10 plays an important role in the composition of the caecal microbiome. Through various enteric pathogen challenges, deficient IL10 expression was associated with enhanced pathogen clearance, but with more severe lesion scores and body weight loss.

Strengths:

Both in vitro and in vivo knock-out abolished and reduced IL10 expression, and broad enteric pathogens were challenged in vivo, and various parameters were examined to evaluate the functional role of IL10 on mucosal immunity.

Weaknesses:

Overexpression of IL-10 either in vitro or in vivo may further support the findings from this study.