Mechanisms of type I interferon production by chicken TLR21.

The innate immune response relies on the ability of host cells to rapidly detect and respond to microbial nucleic acids. Toll-like receptors (TLRs), a class of pattern recognition receptors (PRRs), play a fundamental role in distinguishing self from non-self at the molecular level. In this study, we focused on TLR21, an avian TLR that recognizes DNA motifs commonly found in bacterial genomic DNA, specifically unmethylated CpG motifs. TLR21 is believed to act as a functional homologue to mammalian TLR9. By analysing TLR21 signalling in chickens, we sought to elucidate avian TLR21 activation outputs in parallel to that of other nucleic acid species. Our analyses revealed that chicken TLR21 (chTLR21) triggers the activation of NF-κB and induces a potent type-I interferon response in chicken macrophages, similar to the signalling cascades observed in mammalian TLR9 activation. Notably, the transcription of interferon beta (IFNB) by chTLR21 was found to be dependent on both NF-κB and IRF7 signalling, but independent of the TBK1 kinase, a distinctive feature of mammalian TLR9 signalling. These findings highlight the conservation of critical signalling components and downstream responses between avian TLR21 and mammalian TLR9, despite their divergent evolutionary origins. These insights into the evolutionarily conserved mechanisms of nucleic acid sensing contribute to the broader understanding of host-pathogen interactions across species.

The gut microbiota and its metabolite butyrate shape metabolism and antiviral immunity along the gut-lung axis in the chicken.

The gut microbiota exerts profound influence on poultry immunity and metabolism through mechanisms that yet need to be elucidated. Here we used conventional and germ-free chickens to explore the influence of the gut microbiota on transcriptomic and metabolic signatures along the gut-lung axis in poultry. Our results demonstrated a differential regulation of certain metabolites and genes associated with innate immunity and metabolism in peripheral tissues of germ-free birds. Furthermore, we evidenced the gut microbiota's capacity to regulate mucosal immunity in the chicken lung during avian influenza virus infection. Finally, by fine-analysing the antiviral pathways triggered by the short-chain fatty acid (SCFA) butyrate in chicken respiratory epithelial cells, we found that it regulates interferon-stimulated genes (ISGs), notably OASL, via the transcription factor Sp1. These findings emphasize the pivotal role of the gut microbiota and its metabolites in shaping homeostasis and immunity in poultry, offering crucial insights into the mechanisms governing the communication between the gut and lungs in birds.

Uncovering the core principles of the gut-lung axis to enhance innate immunity in the chicken.

Research in mammals has evidenced that proper colonization of the gut by a complex commensal microbial community, the gut microbiota (GM), is critical for animal health and wellbeing. It greatly contributes to the control of infectious processes through competition in the microbial environment while supporting proper immune system development and modulating defence mechanisms at distant organ sites such as the lung: a concept named 'gut-lung axis'. While recent studies point to a role of the GM in boosting immunity and pathogen resilience also in poultry, the mechanisms underlying this role are largely unknown. In spite of this knowledge gap, GM modulation approaches are today considered as one of the most promising strategies to improve animal health and welfare in commercial poultry production, while coping with the societal demand for responsible, sustainable and profitable farming systems. The majority of pathogens causing economically important infectious diseases in poultry are targeting the respiratory and/or gastrointestinal tract. Therefore, a better understanding of the role of the GM in the development and function of the mucosal immune system is crucial for implementing measures to promote animal robustness in commercial poultry production. The importance of early gut colonization in the chicken has been overlooked or neglected in industrial poultry production systems, where chicks are hampered from acquiring a complex GM from the hen. Here we discuss the concept of strengthening mucosal immunity in the chicken through GM modulation approaches favouring immune system development and functioning along the gut-lung axis, which could be put into practice through improved farming systems, early-life GM transfer, feeding strategies and pre-/probiotics. We also provide original data from experiments with germ-free and conventional chickens demonstrating that the gut-lung axis appears to be functional in chickens. These key principles of mucosal immunity are likely to be relevant for a variety of avian diseases and are thus of far-reaching importance for the poultry sector worldwide.