title: Macrophage polarization in cattle experimentally exposed to Mycobacterium avium subsp. paratuberculosis.
abstract: Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne's disease (JD) in cattle, has significant impacts on the livestock industry and has been implicated in the etiology of Crohn's disease. Macrophages play a key role in JD pathogenesis, which is driven by the manipulation of host immune mechanisms by MAP. A change in the macrophage microenvironment due to pathogenic or host-derived stimuli can lead to classical (M1) or alternative (M2) polarization of macrophages. In addition, prior exposure to antigenic stimuli has been reported to alter the response of macrophages to subsequent stimuli. However, macrophage polarization in response to MAP exposure and its possible implications have not been previously addressed. In this study, we have comprehensively examined monocyte/macrophage polarization and responsiveness to antigens from MAP-exposed and unexposed animals. At 3 years post-exposure, there was a heterogeneous macrophage activation pattern characterized by both classical and alternate phenotypes. Moreover, subsequent exposure of macrophages from MAP-exposed cattle to antigens from MAP and other mycobacterial species led to significant variation in the production of nitric oxide, interleukin-10 and tumour necrosis factor α. These results indicate the previously unreported possibility of changes in the activation state and responsiveness of circulating monocytes/macrophages from MAP-exposed cattle.
authors.affiliation: Faculty of Veterinary Science, The University of Sydney, 425 Werombi Road, Camden, NSW 2570, Australia.
authors.forename: Shyamala
authors.initials: S
authors.lastname: Thirunavukkarasu
authors.affiliation: Faculty of Veterinary Science, The University of Sydney, 425 Werombi Road, Camden, NSW 2570, Australia.
authors.forename: Kumudika
authors.initials: K
authors.lastname: de Silva
authors.affiliation: Faculty of Veterinary Science, The University of Sydney, 425 Werombi Road, Camden, NSW 2570, Australia.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Begg
authors.affiliation: Faculty of Veterinary Science, The University of Sydney, 425 Werombi Road, Camden, NSW 2570, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whittington
authors.affiliation: Faculty of Veterinary Science, The University of Sydney, 425 Werombi Road, Camden, NSW 2570, Australia karren.plain@sydney.edu.au.
authors.forename: Karren M
authors.initials: KM
authors.lastname: Plain
mesh_terms: D000818:Animals; D002417:Cattle; D016753:Interleukin-10 / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D010283:Paratuberculosis / Q000382:microbiology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide
keywords: IL-10; Johne's disease; Mycobacterium avium subspecies paratuberculosis; TNF-α; macrophage polarization; nitric oxide; tolerance