UCD200/206 scleroderma-prone chickens show aberrant innate immune function 2335106

Abstract

Abstract Introduction Non-communicable diseases (e.g., autoimmunity) typically are multifactorial diseases, requiring genetic, immune system, and environmental factors for expression. The UCD200/206 chickens spontaneously develop scleroderma/systemic sclerosis (SSc). The hallmarks of SSc are fibrosis (e.g., dermis of the skin), vasculopathy, and vascular occlusion leading to tissue pathology in highly vascularized organs (lungs and kidneys). Initial observable abnormalities manifest one to two weeks post-hatch and include severe comb swelling and erythema, leading to necrosis and partial or complete loss of the comb. Dermal lesions include swelling, induration, and loss of feathers, and become evident at 3 weeks of age, in the dorsal neck region. In human SSc, there is growing evidence for the role of innate immunity and aberrant innate immune system function in the development of SSc. Methods To determine innate immune response capabilities of UCD200/206 and healthy Leghorn controls, we examined inflammatory responses initiated by innate immunity activators using the minimally invasive growing feather (GF) cutaneous bioassay. Each test-material was administered by intradermal injection multiple GF-pulps of a bird, and GFs collected before-and at various times post-injection for ex vivo analyses. The test-materials were lipopolysaccharide, peptidoglycan, Mycobacterium spp., and Salmonella spp. bacterins. Collected GFs were used for immunofluorescent staining and leukocyte population analysis by flow cytometry, and cytokine mRNA expression analyses by qRT-PCR. Results Aberrant innate inflammatory responses to test-materials, especially to components of gram+ bacteria and particulate antigens were observed, contributing to new knowledge of the temporal, qualitative, and quantitative aspects of inflammatory responses in the SSc-chicken model. Conclusion The spontaneous development of SSc in UCD200/206 chickens provides opportunity to dissect the interactions involved in non-communicable diseases with immunopathology. Funding Source Tyson Professorship in Avian Immunology Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)