Cytokine control of the granulomatous response in Schistosoma mansoni-infected baboons: role of exposure and treatment.
Variations in exposure and treatment may contribute to heterogeneity in immunity and granuloma-induced pathology in human schistosomiasis. To examine this hypothesis, olive baboons were either repeatedly infected with Schistosoma mansoni cercariae or received an equivalent dose in a single infection. They were then cured with praziquantel and reinfected with a single exposure. Serial liver biopsies were obtained throughout the course of the experiment, and cytokine responses by peripheral blood mononuclear cells were measured every 2 to 3 weeks. Reinfection after treatment resulted in a twofold-smaller granuloma size at 6 and 9 weeks after infection compared to the size for the same period after primary infection (P < 0.001) but had no effect at 16 or 19 weeks postinfection. The pattern of exposure did not influence granuloma size. During primary infection schistosome-soluble egg antigen (SEA)-induced cytokine production correlated with granulomatous inflammation. Cytokine levels peaked during the acute infection, declined with chronic infection, and became undetectable after treatment. Reinfection after treatment stimulated a two- to three-fold increase in SEA-specific interleukin-4 (IL-4), IL-5, IL-10, IL-2, and transforming growth factor beta (TGF-beta) production and a marked rise in SEA-specific immunoglobulin E (IgE) and IgG regardless of the type of exposure. Cytokine production was significantly greater in repeatedly exposed animals (P < 0.001). SEA-induced gamma interferon production, however, did not increase with reinfection after treatment. SEA-induced TGF-beta was the only cytokine that remained elevated as the infection become chronic and correlated with diminished hepatic granuloma size, implying its participation in down-modulation. These studies demonstrate that baboons partially retain their ability to down-modulate the granulomatous response after treatment.
Mola
P W
PW
Division of Infectious Diseases, Institute of Primate Research, National Museums of Kenya, Karen, Nairobi, Kenya.
Farah
I O
IO
Kariuki
T M
TM
Nyindo
M
M
Blanton
R E
RE
King
C L
CL
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004195:Disease Models, Animal; D005243:Feces / Q000469:parasitology; D006099:Granuloma / Q000473:pathology*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008099:Liver / Q000473:pathology; D008109:Liver Diseases, Parasitic / Q000188:drug therapy / Q000469:parasitology / Q000473:pathology*; D008297:Male; D010215:Papio; D010270:Parasite Egg Count; D011223:Praziquantel / Q000627:therapeutic use; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000188:drug therapy / Q000469:parasitology / Q000473:pathology*; D012556:Schistosomicides / Q000627:therapeutic use
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D016207:Cytokines; D007074:Immunoglobulin G; D012556:Schistosomicides; D007073:Immunoglobulin E; D011223:Praziquantel