Interleukin-4-deficient BALB/c mice develop an enhanced Th1-like response but control cardiac inflammation following Borrelia burgdorferi infection.
Interleukin-4-deficient BALB/c mice develop an enhanced Th1-like response but control cardiac inflammation following Borrelia burgdorferi infection.
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DOI:
10.1111/j.1574-6968.2000.tb08978.x
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发表时间:
2000-02
影响因子:
2.1
通讯作者:
A. Satoskar;J. Elizondo;G. M. Monteforte;L. Stamm;H. Bluethmann;P. Katavolos;S. Telford
中科院分区:
文献类型:
--
作者:
A. Satoskar;J. Elizondo;G. M. Monteforte;L. Stamm;H. Bluethmann;P. Katavolos;S. Telford
Interleukin-4 has been reported to critically modulate Borrelia burgdorferi infection and Lyme arthritis in experimental murine models. To determine the in vivo role of IL-4 in controlling Lyme carditis, we compared immunological responses and the severity of cardiac inflammation in wild-type BALB/c (IL-4 +/+) and IL-4 deficient BALB/c (IL-4 -/-) mice infected with B. burgdorferi by tick-bite. At day 15 and 30 post-infection IL-4 -/- mice produced significantly greater titers of spirochete-specific IgG2a than the wild-type IL-4 +/+ mice, which produced significantly more spirochete-specific IgG1. Following in vitro antigenic stimulation with B. burgdorferi antigen, splenocytes from infected IL-4 -/- and IL-4 +/+ mice displayed similar magnitudes of proliferative responses at day 15 and 30 post-infection. At day 30 antigen-stimulated splenocytes from infected IL-4 -/- mice, however, produced significantly more IFN-gamma than those derived from similarly infected IL-4 +/+ mice, suggesting that Th1-influenced responses predominated in IL-4 -/- mice. Moreover, inflamed hearts from IL-4 -/- mice displayed higher levels of IFN-gamma and TNF-alpha transcripts as compared to IL-4 +/+ mice. At both time points antigen-stimulated splenocytes from IL-4 +/+ and IL-4 -/- mice produced significant amounts of IL-10 but those from IL-4 +/+ mice produced either no or little IL-4. Histopathology demonstrated typical Lyme carditis in both IL-4 +/+ and IL-4 -/- mice at day 15 and day 30. Although Borrelia-infected IL-4 -/- mice developed a more severe carditis on day 30, the carditis resolved by day 50, as it did in IL4 +/+ mice. These results indicate that although IL-4 may help limit the severity of Lyme carditis, its absence does not preclude resolution of cardiac lesions.