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

Summary 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(I:C), 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 WC1neg 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‐β. 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 WC1neg 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.