Traits associated with innate and adaptive immunity in pigs: heritability and associations with performance under different health status conditions.

There is a need for genetic markers or biomarkers that can predict resistance towards a wide range of infectious diseases, especially within a health environment typical of commercial farms. Such markers also need to be heritable under these conditions and ideally correlate with commercial performance traits. In this study, we estimated the heritabilities of a wide range of immune traits, as potential biomarkers, and measured their relationship with performance within both specific pathogen-free (SPF) and non-SPF environments. Immune traits were measured in 674 SPF pigs and 606 non-SPF pigs, which were subsets of the populations for which we had performance measurements (average daily gain), viz. 1549 SPF pigs and 1093 non-SPF pigs. Immune traits measured included total and differential white blood cell counts, peripheral blood mononuclear leucocyte (PBML) subsets (CD4+ cells, total CD8alpha+ cells, classical CD8alphabeta+ cells, CD11R1+ cells (CD8alpha+ and CD8alpha-), B cells, monocytes and CD16+ cells) and acute phase proteins (alpha-1 acid glycoprotein (AGP), haptoglobin, C-reactive protein (CRP) and transthyretin). Nearly all traits tested were heritable regardless of health status, although the heritability estimate for average daily gain was lower under non-SPF conditions. There were also negative genetic correlations between performance and the following immune traits: CD11R1+ cells, monocytes and the acute phase protein AGP. The strength of the association between performance and AGP was not affected by health status. However, negative genetic correlations were only apparent between performance and monocytes under SPF conditions and between performance and CD11R1+ cells under non-SPF conditions. Although we cannot infer causality in these relationships, these results suggest a role for using some immune traits, particularly CD11R1+ cells or AGP concentrations, as predictors of pig performance under the lower health status conditions associated with commercial farms.

Genetic perspectives on host responses to porcine reproductive and respiratory syndrome (PRRS).

Porcine reproductive and respiratory syndrome (PRRS) is the most economically important disease in pig populations, worldwide. Current research, both in vitro and in vivo, has failed to provide industry with a reliable or effective method to combat the disease. In this paper the present knowledge of the genetics of the host response to porcine reproductive and respiratory syndrome virus (PRRSV) is reviewed. Special reference is made to clinical signs of disease, in vitro and in vivo studies, and evidence of genetic variation in host response to the disease. It is concluded that although clinical signs are numerous, and in vitro and in vivo studies often fail to yield comparable results, there is sufficient evidence of genetic variation in host responses to infection to examine the possibility of breeding for enhanced resistance or tolerance. Advances in genomics have allowed examination of changes in gene expression in response to infection to be examined in tandem with genomewide linkage disequilibrium scans. These advances could allow the possibility for commercial breeding programs to be established, selecting for PRRS resistance or tolerance. When breeding for resistance to one disease, such as PRRS, it could be postulated that the viral control mechanism being exploited could have beneficial effects on resistance to other viral diseases in pigs if, for example, the mechanisms act on primary immune pathways associated with viral replication. Conversely, however, selection for disease resistance could facilitate an increase in susceptibility to other diseases or a reduction in overall productivity. Extensive data recording may be required to guard against such possibilities. Overall, breeding for disease control in pigs is an underutilized tool that could have desirable long-term effects in breeding programs. More research is needed to examine the possible pathways of PRRS resistance so that viable control methods can be found to ease the disease burden and thus increase animal welfare and economic viability.

Innate immune responses to replication of porcine reproductive and respiratory syndrome virus in isolated Swine alveolar macrophages.

Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease caused by a positive RNA strand arterivirus. PRRS virus (PRRSV) interacts primarily with lung macrophages. Identifying the genetic components involved in host resistance/susceptibility would represent an important step forward in the design of disease control programs. In this study, alveolar macrophages derived from five commercial pig lines were used to study the innate immune response to PRRSV infection in vitro. Analysis by flow cytometry has demonstrated that bronchial alveolar lavage fluid (BALF) preparations were almost exclusively composed of alveolar macrophages and that the pigs tested were free from infection. Macrophages from the Landrace line showed significantly reduced virus replication and poor growth of PRRSV during 30 h of infection. By 72 h, PRRSV viral load was down to 2.5 log(10) TCID(50) compared with an average of 5 log(10) TCID(50) for the other breeds tested. These observations suggest that factors intrinsic to the Landrace breed may be responsible for this reduced or delayed response to PRRSV. Preliminary investigation suggests that the PRRSV coreceptor, sialoadhesin, may not be responsible for the Landrace macrophage phenotype as its abundance and localisation were comparable in all the breeds. Strikingly, we found that the reduced or delayed growth of PRRSV was temporally associated with high levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-8 mRNA accumulation and substantial reduction of secretion of IL-8, suggesting a key contributory role for cytokine synthesis and secretion during the innate immune response to PRRSV infection.

[SUPEROXID EXAGERATED PRODUCTION BY NEUTROPHILS OF PATIENTS WITH ACUTE ALCOHOLIC HEPATITIS: THERAPEUTIC IMPLICATIONS] / Exagerada producción de superóxido por los neutrófilos de pacientes con Hepatitis Alcohólica Aguda: Implicancia terapéutica.

Alcoholic hepatitis represents the most severe form of alcoholic liver disease Recent research points to an exaggerated inflammatory response, mediated by neutrophils,as the basic mechanism of liver damage. This entity has a distinctive clinical picture and a characteristic histopathology and a poor outcome.Recent investigation reveals a complex network of intracellular and intercellular communication signals involving hepatocytes, endothelial cells, monocytes, lymphocytes, neutrophils,Ito and Kupffer cells, leading to massive migration of neutrophils from blood to liver.When neutrophils reach the liver, multiple cytokines produced locally by endothelium, hepatocytes and Kupffer cells, up-regulate their function. Activation of neutrophils leads to increased production of oxygen radicals(mainly superoxide)and hydrogen peroxide production.To date there is general agreement that measurement of superoxide production by neutrophils is a reliable way of determining neutrophil function and its activation.Thirty one patients with acute alcoholic hepatitis, twenty with compensated alcoholic liver disease end seventeen controls were studied.Patients with alcoholic hepatitis and alcoholic liver disease were enrolled on admission to the hospital and if they had no features of infection, bleeding or renal failure.The neutrophil stimuli used were opsonized zymosan and fMLP.The production of superoxide was similar in the three groups when neutrophils were not stimulated.After stimulation with opsonized zymosan,there was an increase in the production of superoxide from patients with acute alcoholic hepatitis in comparison to those with alcoholic liver disease and controls. This increase was statistically significant when fMLP was the stimulant(p<0.05). This is a reliable technique that can be use in the evaluation of different therapeutic modalities in acute alcoholic hepatitis