Impaired Th2 development and increased mortality during Schistosoma mansoni infection in the absence of CD40/CD154 interaction.
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.
MacDonald
Andrew S
AS
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Patton
Elisabeth A
EA
La Flamme
Anne C
AC
Araujo
Maria I
MI
Huxtable
Clive R
CR
Bauman
Beverley
B
Pearce
Edward J
EJ
D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D017578:Immunoglobulin Class Switching; D008168:Lung / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D016019:Survival Analysis; D018418:Th2 Cells / Q000276:immunology*
D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D023201:CD40 Ligand