Infection of IL-4-deficient mice with the parasitic nematode Brugia malayi demonstrates that host resistance is not dependent on a T helper 2-dominated immune response

R A Lawrence, J E Allen, W F Gregory, M Kopf, R M Maizels

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Resistance of intact mice to infection with the filarial nematode, Brugia malayi is dependent on the presence of T cells. To investigate the role of Th2 cells in this protection, mice with a targeted disruption of the IL-4 gene were infected with different developmental stages of B. malayi. We examined the phenotypic changes in the immune response and the survival of each stage in these mice. In wild-type mice, adult female worms induce Th2 responses, characterized by antigen-specific IgG1 production, elevated IgE, and marked IL-4 secretion by splenocytes stimulated in vitro with Brugia extract. However, first stage larvae (microfilariae), induce Th1 responses with the appearance of antigen-specific IgG2a, IgG2b, and IgG3 and IFN-gamma secretion by splenocytes. Infection of IL-4-deficient mice revealed a dramatic change in the response to adult worms, with a severe reduction in IgG1 production and a corresponding increase in the production of IgG2a, IgG2b, IgG3, and IFN-gamma release. The switch to Th1-type responses was particularly marked in IL-4-deficient recipients of female worms, which continually release live microfilariae. In the absence of IL-4, down-regulation of the microfilarial-induced Th1 response does not occur. Despite these profound alterations to the immune response in IL-4-deficient mice, survival of infective larvae, adult worms, or microfilariae in the peritoneal cavity was unaffected. In mice, therefore, the prominent Th2-type response elicited by filarial parasites may not be an essential component of the host protective immune response.
Original languageEnglish
Pages (from-to)5995-6001
Number of pages7
JournalThe Journal of Immunology
Volume154
Issue number11
Publication statusPublished - 1995

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Brugia malayi
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Filariasis
  • Immunity, Innate
  • Immunoglobulins
  • Interleukin-4
  • Lymphocyte Activation
  • Lymphokines
  • Male
  • Mice
  • Mice, Knockout
  • Th1 Cells
  • Th2 Cells

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