Impaired Th2 development and increased mortality during Schistosoma mansoni infection in the absence of CD40/CD154 interaction

Andrew S MacDonald, Elisabeth A Patton, Anne C La Flamme, Maria I Araujo, Clive R Huxtable, Beverley Bauman, Edward J Pearce

Research output: Contribution to journalArticlepeer-review

Abstract

The role of CD40/CD154 interaction during infection has primarily focused on pathogens that drive inflammatory Th1 responses. In this study, we show that CD40/CD154 interaction is a fundamental requirement for Th2 response development to the parasitic helminth Schistosoma mansoni. Compared with infected wild-type mice, greatly reduced levels of Th2-associated cytokines were measured both in vitro and in vivo, and no IgE or IgG1 was detected in infected CD154(-/-) mice. In the absence of an overt Th2 response, no exaggerated Th1 response was mounted by CD154(-/-) mice. Infected CD154(-/-) mice suffered severe morbidity and mortality, even though parasitemias in wild-type and CD154(-/-) mice did not differ significantly. These data indicate that CD40/CD154 interaction is required to allow development of a Th2-dominated immune response to S. mansoni and support the view that failure to develop such a response can have fatal consequences.
Original languageEnglish
Pages (from-to)4643-9
Number of pages7
JournalJournal of Immunology
Volume168
Issue number9
Publication statusPublished - 2002

Keywords

  • Animals
  • Antigens, CD40
  • CD40 Ligand
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines
  • Histocompatibility Antigens Class II
  • Immunoglobulin Class Switching
  • Lung
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Schistosomiasis mansoni
  • Survival Analysis
  • Th2 Cells

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