Association of bacterial infection traits with genetic variation at candidate genes for porcine disease resistance

Abstract

We predict that it may be possible to improve pig disease resistance to Salmonella infection by studying genes that control a piglet's initial immune response. The NRAMP1 gene controls susceptibility to multiple pathogens and acts within the macrophage. The BPI gene encodes a neutrophil protein with inhibitory/killing functions against multiple gram-negative bacteria. We investigated NRAMP1 and BPI as candidate genes for contributing to resistance in Salmonella choleraesuis (SC) challenge in pigs. Five NRAMP1 sequence differences (polymorphisms, SNPs) were found, while we cloned and sequenced the full-length BPI gene and identified four polymorphisms at BPI. The effects these polymorphisms have on resistance to infection were tested in two experimental disease studies. In study 1, results showed NRAMP1 and BPI genotypes were associated with decreased fecal bacterial load during infection (P values: < .0006 to < .06). Immune cell numbers were also associated with BPI genotypes. In the second study, many additional immune traits and spleen and liver bacterial counts were collected. The NRAMP1 genotypes were associated with bacterial count in liver (P < .05 and P < .0006) and with polymorphonuclear phagocytes (P values from < .003 to < .05). The BPI genotypes were significantly associated with bacteria uptake by immune cells and with bacterial counts in liver (P<.1) and lymphocyte response post-challenge (P<.0001). These data indicate NRAMP1 and/or BPI gene variation may control, in part, response to Salmonella infection in pigs, and that these differences could be used to identify resistant animals.

Identification of a 5-Methylcytosine Site that may Regulate C/EBPβ Binding and Determine Tissue-Specific Expression of the BPI Gene in Piglets

“…Porcine BPI also has these functions6. Diarrhea and edema, which commonly develop following E.coli F18 infection, are two major causes of mortality in postweaning piglets, and these contribute to immense financial losses in the swine-rearing industry.…”

“…Given its ability to neutralize endotoxin and protect against gram-negative bacteria 19 20 , the BPI has wide application prospects, and can be considered a “super antibiotic”. Porcine BPI also has these functions 6 . Diarrhea and edema, which commonly develop following E.coli F18 infection, are two major causes of mortality in postweaning piglets, and these contribute to immense financial losses in the swine-rearing industry.…”

“…Subsequent in vitro assays showed that antibodies to human BPI enhance the biological activity of porcine BPI5. In recent years, BPI was identified as a candidate gene for disease-resistance breeding in pigs6, and Vandermeer et al . found that recombinant BPI administration protects pigs against endotoxemia-induced acute lung injury7.…”

Polymorphism, Expression of Natural Resistance-associated Macrophage Protein 1 Encoding Gene (&lt;i&gt;NRAMP1&lt;/i&gt;) and Its Association with Immune Traits in Pigs

“…Polymor­phisms of the human Nramp1 gene are sig­nificantly associated with pulmonary Mycobacterium avium complex infection ( Tanaka et al, 2007 ), Crohn’s disease ( Gazouli et al, 2008 ), rheumatoid arthritis ( Ates et al, 2009 ), type 1 diabetes (T1D) ( Yang et al, 2011 ). In pig, the cDNA of NRAMP1 gene has been reported and several single nucleotide polymorphism (SNPs) were also detected and some were found to be associated with the fecal bacteria counts of piglets after challenging with Salmonella cholevasuis ( Tuggle et al, 1997 ; 2005 ).…”

Association of natural resistance-associated macrophage protein 1 polymorphisms with Salmonella fecal shedding and hematological traits in pigs

“…The Nramp1 gene is located on chromosome 15 q23-26 in pigs and has a 15-kilobyte length, with 15 exons and 14 introns [9,10]. The polymorphism of the Nramp1 gene has been related to immunological function [11][12][13], bacterial count [14], diarrhea in pigs [15,16], and post-weaning piglet survivability [11]. One way to use genetics to increase resistance is to correlate them with immunological or hematological characteristics (e.g., cytokine production, leukocyte proliferation, packed cell volume (PCV), red blood cell (RBC) count, and serum levels of immunoglobulin) and the level of fecal Salmonella shedding [11][12][13][14][15][16].…”