Role of IL-4 and IFN-gamma in modulation of immunity to Borrelia burgdorferi in mice.
Because T cells appear to modulate the severity of murine Borrelia burgdorferi infections, we decided to examine the possible involvement of T cell-associated cytokines in disease outcome. Comparison of in vitro B. burgdorferi Ag-induced cytokine production in disease-susceptible and -resistant strains revealed striking differences; spleen cells from susceptible C3H mice produced significantly higher levels of IL-2 and IFN-gamma and lower levels of IL-4 than spleen cells from resistant BALB/c mice. Lymph node responses were even more divergent, with C3H mice producing high levels of IFN-gamma, and BALB/c mice producing little or none. This apparent Th1/Th2 cytokine imbalance was also reflected in vivo, since serum from C3H had significantly higher levels of B. burgdorferi-specific IgG2a Ab and lower levels of IgG1 Ab than serum from BALB/c mice. In vivo studies confirmed the importance of IL-4 in early control of spirochete growth, since treatment of either strain with neutralizing anti-IL-4 mAb led to increased joint swelling and higher spirochete burdens in joints compared with those in control mAb-treated mice. In contrast, IFN-gamma may hinder early control of spirochete growth in susceptible C3H mice, since treatment of mice with neutralizing anti-IFN-gamma mAb reduced both joint swelling and joint spirochete burdens compared with those in control mAb-treated mice. These studies indicate opposing roles for IL-4 and IFN-gamma in the modulation of spirochete growth and disease development in B. burgdorferi-infected mice and suggest that differential cytokine production early in infection may contribute to strain-related differences in susceptibility.
Keane-Myers
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Department of Molecular Microbiology and Immunology, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA.
Nickell
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D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D008193:Lyme Disease / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000276:immunology
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D015847:Interleukin-4; D007371:Interferon-gamma