Integrated Proteotranscriptomics Reveals Differences in Molecular Immunity between Min and Large White Pig Breeds

SIMPLE SUMMARY: The immune system plays a vital role in immune defense, stability, surveillance, tolerance, and regulation. Long-term selection or evolution is an important factor governing the development of disease resistance in pigs. To better understand the molecular mechanisms underlying different levels of disease resistance, we used transcriptomics and proteomics analysis to analyze the immune differences between Chinese and foreign pig breeds and thereby identify critical genes and proteins involved in immune regulation. Key genes involved in these pathways could act as candidates for the discovery of useful polymorphisms that could be included in breeding programs to enable the selection of naturally resistant animals. The results of this study will provide new insights into breeding pigs for disease resistance. ABSTRACT: Long-term selection or evolution is an important factor governing the development of disease resistance in pigs. To better clarify the molecular mechanisms underlying different levels of disease resistance, we used transcriptomics and proteomics analysis to characterize differences in the immunities between six resistant (Min pig) and six susceptible (Large White, LW) pigs which were raised in the same environment. A total of 135 proteins and 791 genes were identified as being differentially expressed between the Large White and Min pig groups. Protein expression clustering and functional analysis revealed that proteins related to immune system process, humoral immune response, the B cell receptor signaling pathway, lymphocyte-mediated immunity, and innate immune responses were more highly expressed in Min pigs. Transcriptome gene set enrichment analysis was used to reveal that pathways of cell adhesion molecules and antigen processing and presentation are significantly enriched in Min pigs. Integrated proteomics and transcriptomics data analysis identified 16 genes that are differentially expressed at both the mRNA and protein levels. In addition, 13 out of these 16 genes were related to the quantitative trait loci of immune diseases, including neural EGFL-like 2 (NELL2) and lactate dehydrogenase B (LDHB), which are involved in innate immunity. Correlation analysis between the genes/proteins and cytokines shows upregulated proteins in LW pigs in association with immunosuppressive/pro-inflammatory cytokines, such as interleukin (IL) 10, IL6, and tumor necrosis factor alpha. This was further validated using parallel reaction monitoring analysis. In summary, we discovered several potential candidate pathways and key genes/proteins involved in determining differences in disease resistance between the two studied pig breeds, which could provide new insights into the breeding of pigs for disease resistance.