Borrelia burgdorferi, an extracellular pathogen, circumvents osteopontin in inducing an inflammatory cytokine response. J Leukoc Biol 2005 May;77(5):710-8
Date
02/08/2005Pubmed ID
15695554DOI
10.1189/jlb.0604356Scopus ID
2-s2.0-18244396334 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
A classic proinflammatory T helper cell type 1 (TH1) response directed against intracellular pathogens includes the cytokine osteopontin, which acts predominantly on macrophages, where it induces the secretion of interleukin (IL)-12 and suppresses the secretion of IL-10. As cell-mediated immune responses play an important role in the resistance to Lyme arthritis, a manifestation of infection by the extracellular pathogen Borrelia burgdorferi, we tested the hypothesis that osteopontin may be required to induce T(H)1 responses and inflammation. The role of osteopontin was tested in vivo and using ex vivo macrophages in B6129F3 mice susceptible to experimental Lyme arthritis. Mice of this genetic background and those fully backcrossed to C57BL/6, which lacked osteopontin expression (spp1-/-), were as susceptible to B. burgdorferi-induced arthritis as littermate controls. Furthermore, equal numbers of spirochetes, as measured by quantitative polymerase chain reaction of the B. burgdorferi gene recA in spp1-/- and B6129F3 wild-type littermates, suggested that susceptibility to infection was not dependent on this cytokine. Neither of the B6129F3 parental mouse strains lacked the ability to secrete osteopontin. spp1-/- mice and controls had immunoglobulin G2 titers, suggestive of a TH1 response. B. burgdorferi was able to directly stimulate the secretion of the proinflammatory cytokines IL-12 and tumor necrosis factor alpha from wild-type and spp1-/- macrophages alike. These results indicate that the usually critical role of osteopontin in the induction of cellular immune responses to intracellular pathogens was circumvented by the ability of the extracellular pathogen B. burgdorferi to induce macrophages directly to produce proinflammatory cytokines.
Author List
Craig-Mylius K, Weber GF, Coburn J, Glickstein LAuthor
Jenifer Coburn PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBorrelia burgdorferi
Cells, Cultured
Interleukin-12
Lyme Disease
Macrophage Activation
Macrophages
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
Osteopontin
Sialoglycoproteins
Tarsal Joints
Th1 Cells
Tumor Necrosis Factor-alpha