Protective responses against skin-dwelling microfilariae of Onchocerca lienalis in severe combined immunodeficient mice

Protective responses against skin-dwelling microfilariae of Onchocerca lienalis in severe combined immunodeficient mice
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DOI:
10.1128/iai.65.7.2846-2851.1997
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发表时间:
1997-07-01
影响因子:
3.1
通讯作者:
Bianco, AE
Bianco, AE
中科院分区:
医学2区
文献类型:
--
作者:
Folkard, SG;Taylor, MJ;Bianco, AE

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Inoculation of severe combined immunodeficient (SCID) mice with microfilariae of Onchocerca lienalis results in a sustained infection of the skin, extending for months beyond the point at which the parasites are eliminated from immunocompetent BALB/c controls. Reconstitution of SCID mice with spleen cells, thymocytes, or CD4(+)-cell-enriched splenocytes from naive BALB/c donors confers the ability to mount a protective immune response, leading to the rapid elimination of microfilariae. High levels of interleukin-5 and low levels of gamma interferon in the sera of reconstituted SCID mice during the destruction of microfilariae suggest that this protective immune response is directed by Th2 lymphocytes, mirroring that observed in immunocompetent controls. Unexpectedly, abbreviation of primary infections of unreconstituted SCID mice with the drug ivermectin induces resistance to reinfection with microfilariae at a level equivalent to that induced in secondarily infected, immunocompetent controls. In contrast to protection mediated by adoptive reconstitution, resistance induced by it iverectin-abbreviated infection occurs in the absence of T cells and in association with negligible levels of serum interleukin-5 and gamma interferon. This paints to the activation of some alternative host defense mechanism that operates after the clearance of therapeutic levels of drng. Such a response could have important implications for the treatment of human onchocerciasis and may go same, way in explaining the long-term suppression of microfilariae observed in patients after treatment with ivermectin.