Borrelia burgdorferi-induced inflammation facilitates spirochete adaptation and variable major protein-like sequence locus recombination.
Spirochete adaptation in vivo is associated with preferential Borrelia burgdorferi gene expression. In this paper, we show that the administration of B. burgdorferi-immune sera to IFN-gammaR-deficient mice that have been infected with B. burgdorferi N40 for 4 days causes spirochete clearance. In contrast, immune sera-mediated clearance of B. burgdorferi N40 is not apparent in immunocompetent mice, suggesting a role for IFN-gamma-mediated responses in B. burgdorferi N40 host adaptation. B. burgdorferi-immune sera also induces clearance of B. burgdorferi N40 that have been passaged in vitro 75 times (B. burgdorferi N40-75), a derivative of B. burgdorferi N40 that does not rapidly adapt in vivo in immunocompetent mice. B. burgdorferi N40-75 produce lower levels of IFN-gamma and IL-12 in mice than does B. burgdorferi N40, and the administration of these cytokines to B. burgdorferi N40-75-infected mice results in an increased spirochetal burden, further indicating that IFN-gamma-mediated events promote B. burgdorferi survival. Differential immunoscreening and RT-PCR demonstrate that IFN-gamma-mediated signals facilitate spirochete recombination at the variable major protein like sequence locus, a site for early antigenic variation in vivo, and that recombination rates by B. burgdorferi N40 are lower in IFN-gammaR-deficient mice than in control animals. These results suggest that the murine immune response can promote the in vivo adaptation of B. burgdorferi.
Anguita
J
J
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Thomas
V
V
Samanta
S
S
Persinski
R
R
Hernanz
C
C
Barthold
S W
SW
Fikrig
E
E
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology; D000954:Antigens, Surface / Q000235:genetics* / Q000276:immunology; D001426:Bacterial Proteins; D001483:Base Sequence; D025065:Borrelia burgdorferi / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004269:DNA, Bacterial / Q000235:genetics*; D005786:Gene Expression Regulation; D007106:Immune Sera; D007121:Immunocompetence; D007249:Inflammation; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D008074:Lipoproteins / Q000235:genetics* / Q000276:immunology; D008193:Lyme Disease / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D011995:Recombination, Genetic; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D000096743:Interferon gamma Receptor
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D007106:Immune Sera; D007371:Interferon-gamma; D018664:Interleukin-12; D008074:Lipoproteins; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C105546:VlsE protein, Borrelia burgdorferi