The large-scale study reported here allowed us to estimate the genetic and phenotypic parameters of numerous ITs measured on pigs bred in the same environment. Innate immunity is represented by 25 traits, humoral-mediated immunity by five traits and cell-mediated adaptive immunity by 18 traits. We have also considered the total number of white blood cells and lymphocytes, and four other haematological traits (RBC, HT, RDW and PLT). Within cell-mediated immunity, we explored both Th1 and Th2 responses by measuring cytokine production. Figure 1 summarizes the traits that we selected to cover immunity globally. These traits include in vivo measures on blood such as quantification of cell populations by hemogram, dosage of circulating immunoglobulins and acute phase proteins, as well as ex vivo measures obtained after in vitro tests such as lymphocyte proliferation, phagocytosis capacity and cytokine production after blood stimulation. All these ITs have been widely studied in humans [25, 26] . The trait typology we have used (Table 1 ) follows a model based on a clear distinction between innate and adaptive immunity, which may be over-simplistic since both immune systems are closely interconnected [27, 28] . Monocytes are involved in innate immunity but are also antigen-presenting cells required for adaptive immunity, and cytokines such as IL12 are at the interface between innate and adaptive immunity. Similarly, the cell-mediated and humoral adaptive immunity subdivision is artificial. For example, IL4 is a cytokine produced by Th2 lymphocytes that is usually classified as part of adaptive cellmediated immunity, whereas it is also involved in antibody production and thus adaptive humoral immunity. In addition, the conventional paradigm that CD4 + ab T lymphocytes differentiate into Th1 and Th2 lineages expressing specific cytokines is collapsing. Indeed, recent studies have revealed that cytokine production by the different CD4 + T cell subsets (Th1, Th2, Th, Th17 and iTreg) is highly flexible, providing new insight into the Th cell plasticity [29] . Nevertheless, although schematic, the approach used in our report provides a comprehensive overview of genetic variation and co-variation across the entire immune spectrum in pigs (Figure 1 ). Table 1 illustrates various ranges of phenotypic variation in the measured immune traits, with most having a CV over 0.5. Such variability has already been reported in large panels of healthy humans [26] , and in previous studies on pigs [2, 16, 17, 30] . For instance, we substantiated the high level of variation of cytokine production previously reported for IL2 production and virusinduced IFNa production in a Swedish Yorkshire population [20] . For innate immunity-related cytokines and IL12, stimulation was performed with a mixture of LPS, PMA and ionomycin. IL8 was the cytokine produced with the highest levels followed by IL1B, TNF, IL12 and lastly IL6. These four cytokines are not expected to be expressed at similar levels at all time points after stimulation and a kinetic study would help to improve comparison of cytokine production levels. Weaker levels of adaptive IR cytokines are observed after LPS stimulation compared to CONA or PMAIONO. These differences could be related to the distinct modes of action of these molecules. Indeed, PMA, a plant-derived functional analog of diacylglycerol, in conjunction with ionomycin, a calcium ionophore produced by Streptomyces conglobatus, and CONA, a lectin originally extracted from the jack-bean Canavalia ensiformis, are known to be potent mitogens of blood lymphocytes [31, 32] . LPS, a major structural component of the outer membrane of gram-negative bacteria, which binds the CD14/ The five first components, which explain more than 50% of the total variance, are in red. B. Plot of the Bayesian Information Criterion (BIC) calculated with different models according to number of clusters. Six models are compared: EII (spherical with equal volume and equal shape), VII (spherical with variable volume and equal shape), EEI (diagonal with equal shape and equal volume), VEI (diagonal with variable shape and equal volume), EVI (diagonal with equal shape and variable volume), VVI (diagonal with variable shape and variable volume). C. First factorial plan (1: first component, 2: second component) with three clusters identified by multivariate normal mixture modelling and model-based clustering taking into account the 32 components (clusters K1, K2 and K3 are in blue, green and red, respectively). doi:10.1371/journal.pone.0022717.g002 TLR4/MD2 receptor complex and promotes the secretion of proinflammatory cytokines, has been extensively used to study innate immune response [33] . We have already shown that transcriptome modifications in peripheral blood mononuclear cells (PBMCs) differ between PMAIONO and LPS stimulation and that PMAIONO and LPS target different cells and cellular pathways [34] . The combination of PMA and ionomycin induces a stronger stimulation that may be related to a higher production of cytokines as detected in the present study. In addition, the lymphocyte proliferation induced by LPS is weaker than that observed with other stimulants, as expected.