Because GenSel does not allow for inclusion of secondary random effects, antibody levels were pre-adjusted for estimates of litter and pen effects obtained from model [2]. to 0.24,+0.05) and for total IgG (0.19+0.05) than for IgM NAb (0.33 to 0.53,+0.07) but maternal effects were larger for IgG NAb (0.41 to 0.52,+0.03) and for total IgG (0.19+0.05) than for IgM NAb (0.00 to 0.10,+0.04). Phenotypically, IgM NAb titers were moderately correlated with each other (average 0.60), as were IgG NAb titers (common 0.42), but correlations between IgM and IgG NAb titers were weak (common 0.09). Phenotypic correlations of total IgG were moderate with NAb IgG (average 0.46) but weak with NAb IgM (common 0.01). Estimates of genetic correlations among NAb showed comparable patterns but with small SE, with estimates averaging 0.76 among IgG NAb, 0.63 among IgM NAb, 0.17 between IgG and IgM NAb, 0.64 between total IgG and IgG NAb, and 0.13 between total IgG and IgM NAb. Phenotypically, pigs that survived experienced slightly higher levels of NAb and total IgG than pigs that died. Genetically, higher THZ1 levels of NAb tended to be associated with greater disease resilience based on lower mortality and fewer parenteral antibiotic treatments. Genome-wide association analyses for NAb titers recognized several genomic regions, with several candidate genes for immune response. == Conclusions == Levels of NAb in blood of healthy young piglets are heritable THZ1 and potential genetic indicators of resilience to polymicrobial disease. Keywords:Disease resilience, Natural antibody, Genetic parameter, Polymicrobial disease challenge, GWAS == Background == The swine industry suffers enormous economic losses as a result of infectious diseases. The porcine reproductive and respiratory syndrome computer virus (PRRSV), for example, costs the U.S. swine industry about $664 million a 12 months [1]. Over the past decade, attention to the genetics of health characteristics in pigs is usually increasing because reducing the economic losses brought on by diseases can greatly improve the production efficiency of pork, along with improving animal welfare and reducing use of antibiotics. Selection for disease resilience, which refers to the ability of an animal to maintain performance when exposed to disease [25], can be an effective strategy to reduce the impact of disease [6]. However, selecting for disease resilience is usually hard because nucleus breeding stock are typically kept in high-health environments. Therefore, the development of indicators of disease resilience that can be measured on young, healthy pigs may lead to practical methods to select for disease resilience. For an indication trait to THZ1 be effective for genetic improvement of disease resilience, it must be heritable, easy to measure at a young age in a high-health environment, and genetically correlated with disease resilience. Natural antibodies (NAb) are THZ1 produced without prior contamination, foreign antigen exposure, or passive immunization [79], and have been shown to be present in blood and milk without prior exposure to pathogens [10,11]. NAb are poly-reactive antibodies that bind different pathogen-associated molecular patterns (PAMPs), are part of the innate immune system, and play important functions in the first line of defense against pathogens [12]. PAMPs are a set of microbial molecules that are shared among related pathogens but vary between groups of pathogens, TLR4 including glycans and glycoconjugates [13]. The innate immune system recognizes PAMPs to activate immune responses and safeguard the host. NAb levels have been measured in vitro using important PAMPs [10,1417], including: lipopolysaccharides (LPS), which are endotoxins found on the cell membranes of gram-negative bacteria, such asEscherichia coliandSalmonellaspp. [18]; lipoteichoic acid (LTA), which is present in Gram-positive bacteria, such asStaphylococcus aureus[19]; peptidoglycan (PDG), which is a polymer that consists of sugars and amino acids that form a mesh-like layer outside the plasma membrane of most bacteria, but with the proportion of PDG being high (90%) in Gram-positive bacteria and low (10%) in Gram-negative bacteria [20]; and keyhole limpet hemocyanin (KLH), which is a large, copper-containing and oxygen-carry protein molecule derived from the hemolymph.