title: Bovine WC1(+) γδ T lymphocytes modify monocyte-derived macrophage responses during early Mycobacterium avium subspecies paratuberculosis infection.
abstract: Following Mycobacterium avium subspecies paratuberculosis (Map) infection, some calves are apparently able to successfully clear the pathogen whereas others become persistently infected; however the reasons for this remain unknown. The importance of innate immunity, and in particular the role of γδ T lymphocytes, during early anti-mycobacterial immune response is recognized but specific mechanisms remain incompletely characterized. The objective of this study was to investigate how bovine WC1(+) γδ T lymphocytes mediate macrophage function during early Map infection. To achieve this objective, Map-infected monocyte-derived macrophages (MDMs) were co-cultured either in direct contact with, or separated by a semi-permeable membrane from, autologous WC1(+) γδ T lymphocytes. Nitrites, IL-17A, IFN-γ, IL-4 and IL-10 from cell culture supernatants were measured. Expression of CD25 on WC1(+) γδ T lymphocytes, expression of MHC-I and MHC-II on MDMs and the viability of Map recovered from MDM cultures 72h after Map infection were also assessed. Map viability was significantly reduced when WC1(+) γδ T lymphocytes were co-cultured in direct contact with Map-infected MDMs. Both MDMs and WC1(+) γδ T lymphocytes generated increased concentrations of IFN-γ and IL-4 in our system, and MDM/WC1(+) γδ T lymphocyte synergism was identified for IFN-γ production. MDMs but not WC1(+) γδ T lymphocytes were a significant source of IL-17A. The presence of WC1(+) γδ T lymphocytes was associated with higher expression of MHC-I on MDMs and increased concentration of nitrites in supernatants 72h after Map infection. In conclusion, this study showed that WC1(+) γδ lymphocytes had differential effects on Map-infected macrophages in vitro.
authors: Department of Pathobiology, Ontario Veterinary College, University of Guelph, Pathobiology/AHL Building 89, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada. Electronic address: mbaquero@uguelph.ca.
authors: Monica M
authors: MM
authors: Baquero
authors: Department of Pathobiology, Ontario Veterinary College, University of Guelph, Pathobiology/AHL Building 89, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada.
authors: Brandon L
authors: BL
authors: Plattner
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology* / Q000382:microbiology; D002478:Cells, Cultured; D005260:Female; D020381:Interleukin-17 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology; D009573:Nitrites / Q000378:metabolism; D010283:Paratuberculosis / Q000276:immunology* / Q000382:microbiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D009573:Nitrites; D015847:Interleukin-4
keywords: Macrophages; Mycobacterium avium subspecies paratuberculosis; WC1(+); γδ T lymphocytes