Differential chemokine and cytokine production by neonatal bovine γδ T-cell subsets in response to viral toll-like receptor agonists and in vivo respiratory syncytial virus infection.

ABSTRACT

γδ T cells respond to stimulation via toll-like receptors (TLR). Bovine γδ T cells express TLR3 and TLR7, receptors that are key for the recognition of viruses such as bovine respiratory syncytial virus (BRSV); however, responses of γδ T cells to stimulation via these receptors, and their role during viral infections, remains unclear. Here, we demonstrate that neonatal bovine γδ T cells exhibit robust chemokine and cytokine production in response to the TLR3 agonist, Poly(IC), and the TLR7 agonist, Imiquimod. Importantly, we observe a similar phenotype in γδ T-cell subsets purified from calves infected with BRSV. Bovine γδ T cells are divided into subsets based upon their expression of WC1, and the response to TLR stimulation and viral infection differs between these subsets, with WC1.1(+) and WC1(neg) γδ T cells producing macrophage inflammatory protein-1α and granulocyte-macrophage colony-stimulating factor, and WC1.2(+) γδ T cells preferentially producing the regulatory cytokines interleukin-10 and transforming growth factor-ß. We further report that the active vitamin D metabolite 1,25-dihydroxyvitamin D3 does not alter γδ T-cell responses to TLR agonists or BRSV. To our knowledge, this is the first characterization of the γδ T-cell response during in vivo BRSV infection and the first suggestion that WC1.1(+) and WC1(neg) γδ T cells contribute to the recruitment of inflammatory populations during viral infection. Based on our results, we propose that circulating γδ T cells are poised to rapidly respond to viral infection and suggest an important role for γδ T cells in the innate immune response of the bovine neonate.