Cutting edge: CD1d deficiency impairs murine host defense against the spirochete, Borrelia burgdorferi.
CD1 molecules can present microbial lipid Ag to T cells, suggesting that they participate in host defense against pathogens. In this study, we examined the role of CD1d in resistance to infection with the Lyme disease spirochete, Borrelia burgdorferi (Bb), an organism with proinflammatory lipid Ag. Bb infection of CD1d-deficient (CD1d(-/-)) mouse strains normally resistant to this pathogen resulted in arthritis. Pathology correlated with an increased prevalence of spirochete DNA in tissues and enhanced production of Bb-specific IgG, including IgG to Ag rapidly down-modulated on spirochetes in vivo. CD1d(-/-) mice exhibited high-titer Bb-specific IgG2a, an isotype commonly induced in disease-susceptible mice but not in the disease-resistant control mice in this study. These results show that CD1d deficiency impairs host resistance to a spirochete pathogen, and are the first example of a mutation that imparts Bb-resistant mice with the Ab and disease profile of a susceptible mouse strain.
Kumar
H
H
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA.
Belperron
A
A
Barthold
S W
SW
Bockenstedt
L K
LK
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000942:Antigens, Bacterial; D018949:Antigens, CD1 / Q000235:genetics*; D055610:Antigens, CD1d; D000954:Antigens, Surface / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D004269:DNA, Bacterial / Q000032:analysis; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D008074:Lipoproteins / Q000276:immunology; D008193:Lyme Disease / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D022123:Lyme Disease Vaccines / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D001743:Urinary Bladder / Q000737:chemistry / Q000382:microbiology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D004269:DNA, Bacterial; D007074:Immunoglobulin G; D008074:Lipoproteins; D022123:Lyme Disease Vaccines; C072045:OspA protein; C079616:OspC protein; C077030:OspB protein, Borrelia burgdorferi