Lack of C3 affects Th2 response development and the sequelae of chemotherapy in schistosomiasis.
The role of the third component of complement (C3) during schistosome infection was investigated using mice deficient in C3. While no effect was observed 8 wk after infection on worm development or liver pathology, Ag-specific Th2-associated cytokine production (IL-13, IL-5, IL-6, and IL-10) was significantly reduced, and IFN-gamma production was enhanced in the absence of C3. IgG1 and IgE, but not IgG2a or IgM, Ab responses were also significantly impaired in infected C3(-/-) mice, suggesting that C3 may play a role in IL-4-mediated Th2 response enhancement during schistosome infection. Furthermore, C3-deficient mice could not effectively clear adult worms after praziquantel (PZQ) treatment and suffered increased morbidity due to the overproduction of proinflammatory mediators following drug administration. However, the ischemic liver damage that normally accompanies PZQ administration in infected wild-type mice was substantially reduced in treated C3-deficient mice, probably due to the absence of dead or dying worms in the livers of these animals. Together these results indicate that C3 enhances Th2 responses during schistosome infection, potentiates PZQ-mediated parasite clearance, and reduces chemotherapy-induced proinflammatory mediator production.
La Flamme
Anne Camille
AC
Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
MacDonald
Andrew S
AS
Huxtable
Clive R
CR
Carroll
Michael
M
Pearce
Edward J
EJ
D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D000947:Antigens, Helminth / Q000276:immunology; D002478:Cells, Cultured; D003176:Complement C3 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D007108:Immune Tolerance / Q000235:genetics; D018836:Inflammation Mediators / Q000097:blood; D008109:Liver Diseases, Parasitic / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009017:Morbidity; D011223:Praziquantel / Q000627:therapeutic use; D012550:Schistosoma mansoni / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology
D000871:Anthelmintics; D000947:Antigens, Helminth; D003176:Complement C3; D016207:Cytokines; D018836:Inflammation Mediators; D011223:Praziquantel