Counter-protective role for interleukin-5 during acute Toxoplasma gondii infection

被引:24
作者
Nickdel, MB
Roberts, F
Brombacher, F
Alexander, J
Roberts, CW
机构
[1] Univ Strathclyde, Strathclyde Inst Biomed Sci, Dept Immunol, Glasgow G4 ONR, Lanark, Scotland
[2] Victoria Infirm, Dept Pathol, Glasgow G42 9TY, Lanark, Scotland
[3] Univ Cape Town, Hlth Fac, Dept Immunol, ZA-7925 Cape Town, South Africa
关键词
D O I
10.1128/IAI.69.2.1044-1052.2001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The role of interleukin-5 (IL-5) during Toxoplasma gondii infection,vas investigated by comparing disease progression in IL-5 gene deficient (IL-5-/-) mice and their wild-type (WT) counterparts on a C57BL/6 background. IL-5-/- mice infected orally with T. gondii were less susceptible to infection than WT mice as demonstrated by reduced mortality rates. Consistent with this data, orally infected IL-5-/- mice had less severe pathological changes in their small intestines than WT mice at 8 days postinfection, At this time, splenocytes and mesenteric lymph node cells derived from IL-5-/- mice produced levels of IL-12, interferon-gamma (IFN-gamma), IL-4, IL-10, and nitric oxide (measured as nitrite) similar to those derived from WT mice when stimulated with Toxoplasma lysate antigen. However, peak serum IL-12 and IFN-gamma levels (at days 6 and 8, respectively) were significantly higher in IL-5-/- mice than in WT mice. In addition, WT mice but not IL-5-/- mice had raised levels of eosinophils in their peripheral blood between days 5 and 8 following infection. Oral administration of Nw-nitro-L-arginine methyl (from day 4 postinfection) increased mortality rates in both IL-5-/- and WT mice, indicating a protective role for nitric oxide during the early stages of oral T, gondii infection. In comparison with oral infection, no difference in mortality was observed between IL-5-/- and WT mice following intraperitoneal infection with T. gondii, with all mice surviving until 35 days postinfection. Similarly, no significant differences were observed in the severity of the meningitis, perivascular cuffing, or number of microglial nodules or parasites in the brains of intraperitoneally infected mice. Together, these results demonstrate a detrimental role for IL-5 during the early stage of oral infection with T, gondii which is associated with increased small-intestine pathology, eosinophilia, and reduced plasma IL-12 and IFN-gamma levels.
引用
收藏
页码:1044 / 1052
页数:9
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