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.
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 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-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 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.
Ruminant Diseases and Immunology Research Unit, National Animal Disease Center, Agricultural Research Service, Ames, IA 50010, USA. Jodi.McGill@ars.usda.gov
Jodi L
JL
McGill
Brian J
BJ
Nonnecke
John D
JD
Lippolis
Timothy A
TA
Reinhardt
Randy E
RE
Sacco
D000634:Aminoquinolines / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002417:Cattle; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions / Q000276:immunology; D000077271:Imiquimod; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000821:virology; D018112:Respiratory Syncytial Virus, Bovine / Q000276:immunology / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D013997:Time Factors; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology* / Q000378:metabolism
D000634:Aminoquinolines; D018925:Chemokines; D016207:Cytokines; C086500:DMBT1 protein, Bos taurus; D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors; D011070:Poly I-C; D000077271:Imiquimod