Abstract
The aim of this work was to explore the possibility of using the presence of tyrosine-phosphorylated macrophage proteins as a phenotype of natural resistance. Tyrosine-phosphorylation of macrophage proteins was investigated in 18 buffaloes, that carried either the resistant, or the non-resistant, Natural Resistance-Associated Macrophage Protein one (NRAMP1) genotype, that various authors have associated with susceptibility to intracellular bacterial diseases. Monocyte-derived macrophages were Interferon-gamma (IFN-γ) stimulated and tyrosine-phosphorylation was assessed by Western blotting. Evidence of phosphorylation after IFN-γ stimulation was shown by 75% of the buffaloes carriers of the resistant genotype, and by 20% of the carriers of the non-resistant genotype (Chisquare value between the groups = 5.44; P = 0.02). The study of the Proteoma of monocyte-derived macrophages might open the way to the genetic control of disease resistance.
Highlights
IntroductionMacrophages are key cells in innate immune response against pathogens; macrophage activation, defined as “acquisition of competence to execute a complex function”, plays an important role in influencing natural resistance to infection
Breeding objectives relating to health, functional traits and welfare need to receive priority in the research programs and selection schemes, but very few reports are available on natural resistant genotype in buffalo [1], where some important diseases cause severe economic losses and pose serious zoonotic threats.Macrophages are key cells in innate immune response against pathogens; macrophage activation, defined as “acquisition of competence to execute a complex function”, plays an important role in influencing natural resistance to infection
Cellular activation involves a variety of post-translational modifications of cytoplasmatic macrophage proteins, that regulate a wide range of cellular functions
Summary
Macrophages are key cells in innate immune response against pathogens; macrophage activation, defined as “acquisition of competence to execute a complex function”, plays an important role in influencing natural resistance to infection. The phosphorylation state, in particular, makes the proteins highly dynamic in controlling the biochemical pathways [2], i.e. the responsible pathways of host innate response in immune-competent cells [3]. Immune system activity is under control of host genetic background [4] and the resistant allelic form of NRAMP1 gene in mouse was positively correlated with a heightened state of phosphorylation of tyrosine residues of protein kinase on macrophages exposed to various biochemical stimuli [5,6]
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