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Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 5/26/2016 Publication Date: 6/4/2016 Citation: Dawson, H.D., Smith, A.D., Chen, C.T., Urban Jr, J.F. 2016. An in-depth comparison of the porcine, murine and human inflammasomes; lessons from the porcine genome and transcriptome. Veterinary Microbiology. pii:S0378-1135(16)30137-7. doi: 10.1016/j.vetmic.2016.05.013. Interpretive Summary: Emerging evidence suggests that swine are a scientifically acceptable intermediate species between rodents and humans to model immune function relevant to humans. The swine genome has recently been sequenced and several preliminary structural and functional analyses of the genes involved in the porcine immune response have been published. Herein we provide an expanded analysis of those genes using an improved assembly of the porcine genome. Comparisons of the expansion or contraction of genes that are present in each genome indicated more similar rates and classes of genes in humans and pigs than in mice; however, several novel porcine or artiodactyl-genes were identified. The conservation of homology and structural motifs of protein encoding genes that are present in all of the genomes revealed that the overall mean similarity to human proteins was significantly higher for pigs compared to mice. Despite these similarities, two out of four central pathways involved in recognition of pathogens found to be missing in pigs. Pig macrophage polarization in response to interferon-g (IFN-g and lipopolysaccharide (LPS) was assessed, via measuring mRNA levels using next generation sequencing. Our analysis revealed predominantly human-like responses; however, some mouse-like responses were observed, as well as induction of numerous pig or artiodacyl-specific genes. This work supports using swine to model both human immunological and inflammatory responses to infection. However, caution must be exercised as pigs differ from humans in several fundamental pathways. Technical Abstract: Emerging evidence suggests that swine are a scientifically acceptable intermediate species between rodents and humans to model immune function relevant to humans. The swine genome has recently been sequenced and several preliminary structural and functional analysis of the porcine immunome have been published. Herein we provide an expanded in silico analysis using an improved assembly of the porcine transcriptome that provides an in-depth analysis of genes that are related to inflammasomes, responses to Toll-like receptor ligands, and M1 macrophage polarization. Comparisons of the expansion or contraction of orthologous gene families indicated more similar rates and classes of genes in humans and pigs than in mice; however, several novel porcine or artiodactyl-specific paralogs or pseudogenes were identified. The conservation of homology and structural motifs of orthologs revealed that the overall mean similarity to human proteins was significantly higher for pigs compared to mice. Despite these similarities, two out of four canonical inflammsome pathways that included the Absent in melanoma 2 (AIM2) and NLR family and CARD domain containing 4 (NLRC4) pathways were found to be missing in pigs. Pig M1 Mf polarization in response to interferon-g (IFN-g and lipopolysaccharide (LPS) was assessed, via the transcriptome, using next generation sequencing. Our analysis revealed predominantly human-like responses; however, some mouse-like responses were observed, as well as induction of numerous pig or artiodacyl-specific genes. This work supports using swine to model both human immunological and inflammatory responses to infection. However, caution must be exercised as pigs differ from humans in several fundamental pathways. |
