Understanding the role of host and pathogen factors in the outcome of infections in chickens to develop knowledge-driven strategies for disease control.
Zoonotic bacterial infections of poultry
Bacteria commonly found in poultry such as Salmonella and Campylobacter can transmit through the food chain and cause gastrointestinal disease in humans. Avian pathogenic Escherichia coli (APEC) are associated with severe respiratory and systemic disease in poultry and may also be zoonotic as they are closely related to E. coli that cause sepsis, meningitis and urinary tract infections in humans. Research at the Roslin institute has investigated both bacterial and host factors that influence the persistence of these organisms in poultry, their ability to produce disease and the basis of avian resistance. For example, using crosses of inbred lines that differ in resistance to Salmonella and Campylobacter it has been possible to map regions of the avian genome associated with heritable resistance1,2. Recently Chintoan-Uta and colleagues also investigated the role of caecal microbiota in resistance to colonization by Campylobacter jejuni in our inbred chicken lines3. Our researchers have also assigned roles to thousands of Salmonella genes that colonise poultry, for example via screening of libraries of transposon mutants4.
Understanding natural and vaccine-mediated immunity
Developing an understanding of immune responses to specific pathogens in poultry can help vaccine development. Mucosal surfaces, such as those present in the gut and lungs are a common route of infection for economically important pathogens in poultry. Researchers at the Roslin Institute have developed improved methods to understand basic host-pathogen interactions at this route of infection, that has the potential to improve mucosal vaccination for these pathogens. For example, a novel tool has been developed to examine host–pathogen interaction in the chicken lung. By using CSF1R-eGFP and CSF1R-mApple transgenic chickens, Bryson and colleagues have shown that lung samples taken from chickens can be used in vitro to examine infection progression and could help find new treatments5. By combining CSF1R reporter chickens with the use of fluorescently-labelled bacteria, it has been possible to visualise the cell types targeted by E. coli and Salmonella in poultry and to observe the functions of immune cells in situ6,7. Through understanding the role of pathogen factors in chickens, we can also evaluate novel subunit, glycoconjugate, live-attenuated and vectored vaccines.
Genome engineering and host resistance
Roslin researchers have used genetic modification to produce chickens that while susceptible to infection with avian influenza virus, did not pass on the virus to other birds8. Recent advances have used gene-editing techniques in lab-grown chicken cells to remove a section of DNA responsible for producing ANP32A – a protein that flu viruses hijack to replicate themselves. The virus was no longer able to grow inside cells with the genetic change9. Future research based on this work aims to produce gene-edited chickens that are resistant to avian influenza.
- Psifidi, A. et al. The genomic architecture of resistance to Campylobacter jejuni intestinal colonisation in chickens. BMC Genomics 17, 293 (2016).
- Fife, M. S. et al. Genome-wide SNP analysis identifies major QTL for Salmonella colonization in the chicken. Anim. Genet. 42, 134–140 (2011).
- Chintoan-Uta, C. et al. Role of caecal microbiota in the differential resistance of inbred chicken lines to colonization by Campylobacter jejuni. Appl. Environ. Microbiol. (2020). doi:10.1128/aem.02607-19
- Chaudhuri, R. R. et al. Comprehensive assignment of roles for Salmonella typhimurium genes in intestinal colonization of food-producing animals. PLoS Genet. 9, e1003456 (2013).
- Bryson, K. J. et al. Precision cut lung slices: A novel versatile tool to examine host-pathogen interaction in the chicken lung. Vet. Res. 51, 1–16 (2020).
- Alber, A. et al. Avian pathogenic Escherichia coli (APEC) strain-dependent immunomodulation of respiratory granulocytes and mononuclear phagocytes in CSF1R-reporter transgenic chickens. Front. Immunol. 10, 3055 (2020).
- Balic, A. et al. Antigen sampling CSF1R-expressing epithelial cells are the functional equivalents of mammalian m cells in the avian follicle-associated epithelium. Front. Immunol. 10, 2495 (2019).
- Lyall, J. et al. Suppression of avian influenza transmission in genetically modified chickens. Science. 331, 223–226 (2011).
- Long, J. S. et al. Species specific differences in use of ANP32 proteins by influenza A virus. Elife 8, (2019).