Toll-like receptor 2 is required for innate, but not acquired, host defense to Borrelia burgdorferi.
Borrelia burgdorferi lipoproteins activate inflammatory cells through Toll-like receptor 2 (TLR2), suggesting that TLR2 could play a pivotal role in the host response to B. burgdorferi. TLR2 does play a critical role in host defense, as infected TLR2(-/-) mice harbored up to 100-fold more spirochetes in tissues than did TLR2(+/+) littermates. Spirochetes persisted at extremely elevated levels in TLR2-deficient mice for at least 8 wk following infection. Infected TLR2(-/-) mice developed normal Borrelia-specific Ab responses, as measured by quantity of Borrelia-specific Ig isotypes, the kinetics of class switching to IgG, and the complexity of the Ags recognized. These findings indicate that the failure to control spirochete levels in tissues is not due to an impaired acquired immune response. While macrophages from TLR2(-/-) mice were not responsive to lipoproteins, they did respond to nonlipoprotein components of sonicated spirochetes. These TLR2-independent responses could play a role during the inflammatory response to B. burgdorferi, as infected TLR2(-/-) mice developed greater ankle swelling than wild-type littermates. Thus, while TLR2-dependent signaling pathways play a major role in the innate host defense to B. burgdorferi, both inflammatory responses and the development of the acquired humoral response can occur in the absence of TLR2.
Wooten
R Mark
RM
Department of Pathology, University of Utah, 50 North medical Drive, Salt Lake City, UT 84132, USA.
Ma
Ying
Y
Yoder
R Alyson
RA
Brown
Jeanette P
JP
Weis
John H
JH
Zachary
James F
JF
Kirschning
Carsten J
CJ
Weis
Janis J
JJ
D000818:Animals; D000843:Ankle Joint / Q000382:microbiology / Q000473:pathology; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001428:Bacterial Vaccines; D001899:Borrelia Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D025065:Borrelia burgdorferi / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004269:DNA, Bacterial / Q000032:analysis; D029721:Drosophila Proteins; D007700:Kinetics; D008074:Lipoproteins; D022123:Lyme Disease Vaccines / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D004269:DNA, Bacterial; D029721:Drosophila Proteins; D008074:Lipoproteins; D022123:Lyme Disease Vaccines; D008562:Membrane Glycoproteins; C072045:OspA protein; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors