Time course study of the response to LPS targeting the pig immune gene networks

Abstract

BackgroundStress is a generic term used to describe non-specific responses of the body to all kinds of challenges. A very large variability in the response can be observed across individuals, depending on numerous conditioning factors like genetics, early influences and life history. As a result, there is a wide range of individual vulnerability and resilience to stress, also called robustness. The importance of robustness-related traits in breeding strategies is increasing progressively towards the production of animals with a high level of production under a wide range of climatic conditions and management systems, together with a lower environmental impact and a high level of animal welfare. The present study aims at describing blood transcriptomic, hormonal, and metabolic responses of pigs to a systemic challenge using lipopolysaccharide (LPS). The objective is to analyze the individual variation of the biological responses in relation to the activity of the HPA axis measured by the levels of plasma cortisol after LPS and ACTH in 120 juvenile Large White (LW) pigs. The kinetics of the response was measured with biological variables and whole blood gene expression at 4 time points. A multilevel statistical analysis was used to take into account the longitudinal aspect of the data.ResultsCortisol level reaches its peak 4 h after LPS injection. The characteristic changes of white blood cell count to LPS were observed, with a decrease of total count, maximal at t=+4 h, and the mirror changes in the respective proportions of lymphocytes and granulocytes. The lymphocytes / granulocytes ratio was maximal at t=+1 h. An integrative statistical approach was used and provided a set of candidate genes for kinetic studies and ongoing complementary studies focused on the LPS-stimulated inflammatory response.ConclusionsThe present study demonstrates the specific biomarkers indicative of an inflammation in swine. Furthermore, these stress responses persist for prolonged periods of time and at significant expression levels, making them good candidate markers for evaluating the efficacy of anti-inflammatory drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-4363-5) contains supplementary material, which is available to authorized users.

2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia

“…This is consistent with previous studies, which have shown that the dynamics of metabolic pathways and metabolites (e.g. glucose, amino acids, and lipids) are significantly altered in response to LPS and sepsis (Kamisoglu et al, 2013(Kamisoglu et al, , 2015Terenina et al, 2017;Fitzpatrick et al, 2018). Moreover, in septic patients 2HG levels were also reduced in both urine and serum samples.…”

Effects of divergent selection upon adrenocortical activity on immune traits in pig

“…We next evaluated metabolic and immune responses to in vivo LPS challenge at week 8. In both lines, LPS induced activation of the HPA axis, as shown by the elevation of plasma cortisol levels following injection, confirming previous observations in unselected pigs [19]. The LPS-induced metabolic changes also consisted in an increase in free fatty acid release and bilirubinaemia associated to a decrease in glycaemia, probably due to increased glycolysis and decreased neoglucogenesis.…”

“…At week 6, hematologic and immune parameters were analysed on blood samples collected from 9 to 10 a.m (Experiment 1) . Two weeks later, a kinetic response to intra-muscular LPS injection (15 μg/kg in the neck muscles) was performed on the same animals with blood samples collected just before (t0, between 9 and 10 a.m. ) and 1, 4 and 24 h after LPS administration as previously described [19] (Experiment 2).…”

“…For experiment 2, cortisol, TNFα, IL-6, white blood cells and platelets data were transformed into their logarithmic scores for normalisation. The square root transformation was used for NEFA (non-esterified fatty acids) levels [19]. For each parameter, the effect of HPA activity, time, and their interaction was tested in a two-way analysis of variance with repeated measures for the time factor.…”

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

“…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 [23–28]. LPS stimulation can cause many physiological and behavioral changes, including elevated body temperature, dramatic hemodynamic, increased cytokine levels, reduced feed intake, and altered metabolism [29–32].…”