T cell infiltration is associated with increased Lyme arthritis in TLR2-/- mice.
C57BL/6 mice deficient in TLR2 develop more severe arthritis following infection with Borrelia burgdorferi than do wild-type C57BL/6 mice, and this increase is suppressed by the simultaneous presence of the scid mutation. This suggested a requirement for lymphocytes in the development of subacute Lyme arthritis in TLR2(-/-) mice, a feature not commonly associated with this arthritis. The increased pathology of B. burgdorferi-infected TLR2(-/-) mice was also accompanied by an increase in mononuclear cell infiltration. In this study, T cells were found to be responsible for the increase in mononuclear cells in infected TLR2(-/-) C3H mice. Accordingly, transcripts for the IFN-inducible T cell chemokines, CXCL9 and CXCL10, were greatly enhanced in joint tissue from TLR2(-/-) mice, as were transcripts for a prototypical IFN-inducible gene IFN-gamma-induced GTPase (igtp). Treatment of murine synovial cells with sonicated B. burgdorferi resulted in induction of transcripts for chemokines and other IFN-inducible genes, irrespective of the presence of TLR2. The presence of T lymphocytes greatly enhanced the transcriptional response of synovial cells. These results suggest that the increased inflammatory cell infiltration in TLR2(-/-) C3H mice is the result of localized overproduction of T cell attracting chemokines.
Wang
Xiaohui
X
Department of Pathology, University of Utah, Salt Lake City, UT 84112-5650, USA.
Ma
Ying
Y
Yoder
Alyson
A
Crandall
Hillary
H
Zachary
James F
JF
Fujinami
Robert S
RS
Weis
John H
JH
Weis
Janis J
JJ
D000818:Animals; D000843:Ankle Joint / Q000276:immunology / Q000473:pathology; D025065:Borrelia burgdorferi / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D054370:Chemokine CXCL9 / Q000096:biosynthesis; D020558:GTP Phosphohydrolases / Q000096:biosynthesis; D008193:Lyme Disease / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000276:immunology*
D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D020558:GTP Phosphohydrolases; C101131:Igtp protein, mouse