Abstract
Transcription factors (TFs) modulate genes involved in cell-type-specific proliferative and migratory properties, metabolic features, and effector functions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogen agents in the porcine industry; however, TFs have been poorly studied during the course of this disease. Therefore, we aimed to evaluate the expressions of the TFs T-bet, GATA3, FOXP3, and Eomesodermin (EOMES) in target organs (the lung, tracheobronchial lymph node, and thymus) and those of different effector cytokines (IFNG, TNFA, and IL10) and the Fas ligand (FASL) during the early phase of infection with PRRSV-1 strains of different virulence. Target organs from mock-, virulent Lena-, and low virulent 3249-infected animals humanely euthanized at 1, 3, 6, 8, and 13 days post-infection (dpi) were collected to analyze the PRRSV viral load, histopathological lesions, and relative quantification through reverse transcription quantitative PCR (RT-qPCR) of the TFs and cytokines. Animals belonging to both infected groups, but mainly those infected with the virulent Lena strain, showed upregulation of the TFs T-bet, EOMES, and FOXP3, together with an increase of the cytokine IFN-γ in target organs at the end of the study (approximately 2 weeks post-infection). These results are suggestive of a stronger polarization to Th1 cells and regulatory T cells (Tregs), but also CD4+ cytotoxic T lymphocytes (CTLs), effector CD8+ T cells, and γδT cells in virulent PRRSV-1-infected animals; however, their biological functionality should be the object of further studies.
Highlights
The correct functioning of the cell-mediated immune system is a major branch in the successful eradication of viruses [1]
Transcription factors (TFs) regulate the development of different immune cell subsets by activating or repressing genes that are critical to cellular identity [3]
We evaluated the expressions of different TFs (T-bet, GATA3, FOXP3, and EOMES) through reverse transcription quantitative PCR (RT-qPCR) and the associated cytokine profiles during infection with Porcine reproductive and respiratory syndrome virus (PRRSV)-1 strains of different virulence in target organs
Summary
The correct functioning of the cell-mediated immune system is a major branch in the successful eradication of viruses [1]. Naive CD4+ T cells undergo several rounds of division and become polarized into different effector T helper (Th) cell subsets [2] This process is tightly regulated by a set of transcription factors (TFs) that, together with cytokines in the priming. Minor expression of the TF FOXP3 has been reported in CD8+ T cells [10] Another T-box TF family member, Eomesodermin (EOMES), is involved in the polarization of cytotoxic CD4 Th1 cells, known as CD4 cytotoxic T lymphocytes (CD4 CTLs), which yield the release of cytolytic effector molecules such as granzyme B and perforin and/or the ligation of cell death surface ligands such as FasL [2, 11,12,13]. They have been related with other functions beyond the regulation of CD4 T-cell differentiation, such as the regulation of cytotoxic CD8+ T-cell activity and memory differentiation [1]
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