Acute systemic inflammatory response to lipopolysaccharide stimulation in pigs divergently selected for residual feed intake

摘要

BackgroundFeed efficiency in pigs is a trait of economic, environmental and societal importance. One increasingly accepted measure of feed efficiency is residual feed intake (RFI), which is defined as the difference between an individual animal’s observed and expected feed intake for growth and maintenance [1]. Thus pigs with a low RFI are more feed efficient than those with a high RFI. Pilot studies of divergent selection for RFI in pigs showed that RFI responds well to genetic selection [2,3,4].Compared to high-RFI pigs, pigs selected for low RFI have reduced feed intake, but similar rate of growth [2,3,4]. This difference occurs likely because the low-RFI pigs are more efficient in allocating resources for production and maintenance [5]. The immune response is a nutrient- and energy-demanding biological process and directly relates to pig health and performance [6, 7]. Thus, one interesting question is whether improving feed efficiency by selection for low RFI affects the animal’s ability to respond to immune challenges. Based on resource allocation theory [5], selection for high feed efficiency is expected to compromise the animal’s capacity to handle immune stimulation, such as the response that occurs during infectious diseases [8]. This has been confirmed in studies on chickens and beef cattle, where selection for increased feed efficiency indeed negatively affected their immune system [9].Several experiments have investigated the potential side effects of selection for divergent RFI phenotypes on the immune response in pigs. First, a study of healthy pigs from the divergently selected RFI lines at Iowa State University (ISU) [2,3,4], from which representatives were used in the current study, showed that the low-RFI line had lower numbers of monocytes, lymphocytes, and basophils, but a higher hemoglobin concentration and red blood cell volume compared to the high-RFI line [10]. Second, based on results from an experimental infection with the porcine reproductive and respiratory syndrome virus (PRRSV) in pigs from the ISU RFI lines [2,3,4], Dunkelberger et al. [11] reported that pigs from the low-RFI line had a lower viral RNA load in the blood, a faster humoral immune response to PRRSV, and were less affected in terms of reduced growth rate than pigs from the high-RFI line. Third, in a parallel divergent selection experiment conducted at the French National Institute for Agricultural Research (INRA), the low-RFI line had a lower basal expression of many genes involved in immune and inflammatory response than the high-RFI line [12, 13]. Fourth, to test the immune response in the divergently selected RFI lines developed by INRA, piglets from both lines were challenged with the Complete Freund’s Adjuvant (CFA) to induce a non-infectious pneumonia [14,15,16,17]. This work showed that both RFI lines handled the inflammatory challenge similarly, but did so by adopting different metabolic strategies [15]. Interestingly, the protein abundance of inflammatory cytokines was lower in the low-RFI line in multiple tissues involved in the immune response 1 week after CFA injection [16]. Lastly, Vigros et al. [18] examined the expression profiles of a set of target genes related to intestinal inflammation in pigs with extremely divergent RFI phenotypes, both before and after an ex vivo LPS exposure of ileal and colonic tissue explants. No differentially expressed genes were detected in the un-stimulated explants. However, the mRNA levels of several proinflammatory cytokines (IL8, IL1, IL6, TNFα, IFNγ) and SOCS3 were lower in the low-RFI than the high-RFI explants following LPS challenge [18]. These authors proposed that low-RFI pigs may adopt an energy saving mechanism during intestinal responses to an immune challenge [18]. Taken together, although no significant negative side effects of selection for increased feed efficiency based on reduced RFI on the immune response in pigs have been detected, little is known about the effect of selection for RFI on the global transcriptomic profiles during the course of acute systemic inflammatory response in pigs.As a major component of the outer membrane of most gram-negative bacteria [19], LPS has been widely used in vertebrates as an inflammatory immunostimulant. In vertebrates, LPS induces inflammatory response mainly via the TLR4-dependent NFκB signaling pathway [20, 21], although a TLR4-independent host response to LPS has also been identified [22]. Thousands of genes, including many pro-inflammatory and anti-inflammatory cytokines and chemokines, have been shown to be involved in the LPS-induced inflammatory response in multiple vertebrates, including pigs [23,24,25,26,27,28]. LPS stimulation can cause many physiological and behavioral changes, including elevated body temperature, dramatic hemodynamic, increased cytokine levels, reduced feed intake, and altered metabolism [29,30,31,32].The objective of this study was to determine whether divergent selection for RFI s