Mercury exposure as a model for deviation of cytokine responses in experimental Lyme arthritis: HgCl2 treatment decreases T helper cell type 1-like responses and arthritis severity but delays eradication of Borrelia burgdorferi in C3H/HeN mice.
Lyme borreliosis is a complex infection, where some individuals develop so-called 'chronic borreliosis'. The pathogenetic mechanisms are unknown, but the type of immune response is probably important for healing. A strong T helper cell type 1 (Th1)-like response has been suggested as crucial for eradication of Borrelia and for avoiding development of chronic disease. Many studies aimed at altering the Th1/Th2 balance in Lyme arthritis employed mice deficient in cytokine genes, but the outcome has not been clear-cut, due possibly to the high redundancy of cytokines. This study aimed at studying the importance of the Th1/Th2 balance in murine Borrelia arthritis by using the Th2-deviating effect of subtoxic doses of inorganic mercury. Ninety-eight C3H/HeN mice were divided into four groups: Borrelia-infected (Bb), Borrelia-infected exposed to HgCl(2) (BbHg), controls exposed to HgCl(2) alone and normal controls. Mice were killed on days 3, 16, 44 and 65 post-Borrelia inoculation. Arthritis severity was evaluated by histology, spirochaetal load determined by Borrelia culture, IgG2a- and IgE-levels analysed by enzyme-linked immunosorbemt assay (ELISA) and cytokine-secreting cells detected by enzyme-linked immunospot (ELISPOT). BbHg mice showed less severe histological arthritis, but delayed eradication of spirochaetes compared to Bb mice, associated with increased levels of IgE (Th2-induced) and decreased levels of IgG2a (Th1-induced), consistent with a Th2-deviation. Both the numbers of Th1 and Th2 cytokine-secreting cells were reduced in BbHg mice, possibly explained by the fact that numbers of cytokine-secreting cells do not correlate with cytokine concentration. In conclusion, this study supports the hypothesis that a Th1-like response is required for optimal eradication of Borrelia.
Ekerfelt
C
C
Division of Clinical Immunology, and Unit of Autoimmunity and Immune Regulation, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, University Hospital, Linköping, Sweden. Christina.Ekerfelt@imk.liu.se
Andersson
M
M
Olausson
A
A
Bergström
S
S
Hultman
P
P
D000818:Animals; D001170:Arthritis, Infectious / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D025065:Borrelia burgdorferi / Q000302:isolation & purification; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007596:Joints / Q000473:pathology; D008193:Lyme Disease / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D008627:Mercuric Chloride / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology
D007074:Immunoglobulin G; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D008627:Mercuric Chloride; D007371:Interferon-gamma