Control of parasitemia and survival during Trypanosoma brucei brucei infection is related to strain dependent ability to produce interleukin-4

M Bakhiet, L Jansson, P Büscher, R Holmdahl, K Kristensson, T Olsson

    Research output: Contribution to journalA1: Web of Science-article

    Abstract

    We studied non-MHC gene-dependent expression of a number of cytokines in relation to host defense and survival during Trypanosoma brucei brucei (Tbb) infection in mice. In particular, the role of IL-4 was explored with use of genomically IL-4-disrupted mice and in vivo Ab blocking. Splenocytes from MHC-identical B10.Q (relatively resistant) mice showed day 5 postinfection higher numbers of IL-4 mRNA expressing cells than C3H.Q (highly susceptible). A trypanosome-derived lymphocyte triggering factor, which is released by Tbb to polyclonally activate CD8+ T cells, stimulated naive splenocytes in vitro to a higher IL-4 response in B10.Q than in C3H.Q mice. The C3H.Q mice developed an extremely high parasitemia, showed a low Ab response against the variant surface glycoprotein (VSG), and had a mean survival time of 42 days. Conversely, B10.Q mice had lower parasitemia, mounted higher anti-VSG response, and had a mean survival time of 56 days. Deletion of the IL-4 gene had no influence on the infection in C3H.Q mice, while in B10.Q mice the deletion was associated with lower anti-VSG Ab levels and higher parasitemia. Paradoxically, B10.Q mice with disrupted IL-4 gene survived longer than the wild type. Anti-IL-4 Ab-blocking experiments in vivo displayed an enhanced parasitemia and prolonged survival in infected B10.Q mice. We conclude that 1) a non-MHC gene-related and CD8+-dependent ability to produce IL-4 partly determines the susceptibility to Tbb infection; and 2) IL-4, although involved in controlling the levels of parasitemia by its effects on immunoglobulin synthesis, also can have toxic effects on the animals.
    Original languageEnglish
    JournalJournal of Immunology
    Volume157
    Pages (from-to)3518-3526
    ISSN0022-1767
    Publication statusPublished - 1996

    Keywords

    • B780-tropical-medicine
    • Protozoology
    • Trypanosoma brucei brucei
    • Parasitemia
    • Immunology
    • Experimental
    • Interleukin

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