Recombinant IL-4 treatment augments resistance to Borrelia burgdorferi infections in both normal susceptible and antibody-deficient susceptible mice.
Recent evidence suggests that T cells and their associated cytokines critically influence outcome in mice experimentally infected with Borrelia burgdorferi (Bb), the causative agent of human Lyme disease. In vivo T cell subset and cytokine depletion studies suggest that CD4+ T cell-derived IL-4 plays a critical role in control of spirochete growth in vivo, whereas CD8+ T cell-derived IFN-gamma appears to promote disease, particularly in susceptible mouse strains. To further investigate the immunologic basis of protection and the role of IL-4, we have examined the effects of early rIL-4 treatment on outcome in susceptible mice infected with Bb. In this study, we show that administration of rIL-4 to susceptible C3H mice during the first week of infection with Bb leads to early control of their infections, as evidenced by significant reductions in joint swelling at wk 5, 6, and 7 postinfection, and in the numbers of spirochetes recovered from their joints and skin at wk 7 when compared with sham-treated mice. Increased resistance in rIL-4-treated mice was accompanied by significant reductions in their in vitro splenic Bb-specific IFN-gamma responses and in serum levels of specific IgG2a and IgG3 Abs and significant increases in specific IgG1 Abs. We also show that the inherent susceptibility of Ab-deficient, C57BL/6-IgM knockout (B6-MKO) mice to Rh infection is intermediate relative to C57BL/6 severe combined immunodeficient (B6-SCID) mice (susceptible) or normal C57BL/6 mice (resistant), confirming the importance of both Ab-dependent and Ab-independent, T cell-dependent immune mechanisms in control of Bb infections. The additional finding that early treatment with rIL-4 significantly reduced the severity of Bb infections in B6-MKO mice indicates that IL-4 may augment anti-spirochetal immunity via an Ab-independent mechanism.
Keane-Myers
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A
Department of Molecular Microbiology and Immunology, The John Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA.
Maliszewski
C R
CR
Finkelman
F D
FD
Nickell
S P
SP
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D015748:Borrelia burgdorferi Group / Q000276:immunology* / Q000302:isolation & purification; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D011994:Recombinant Proteins / Q000494:pharmacology; D013045:Species Specificity; D013997:Time Factors
D000907:Antibodies, Bacterial; D011994:Recombinant Proteins; D015847:Interleukin-4