Mice deficient for 5-lipoxygenase, but not leukocyte-type 12-lipoxygenase, display altered immune responses during infection with Schistosoma mansoni.
Periovular granuloma formation during Schistosoma mansoni infection is a complex, multifaceted immunologic response. Products of arachidonic acid metabolism have been shown to contribute to this response through studies in which general inhibitors of lipoxygenase function reduce granulomatous inflammation. To determine which lipoxygenases are important for granuloma development in schistosomiasis, wild type mice or mice deficient for 5-lipoxygenase (5-LO) or "leukocyte-type" 12-lipoxygenase (12-LO) were infected with S. mansoni and studied for responses to schistosome eggs and egg antigens. At the acute stage of infection, when granuloma formation is usually maximal, 5-LO deficient mice developed smaller granulomas around liver-deposited schistosome eggs compared with wild type or 12-LO deficient mice. 5-LO mice also displayed less antibody-mediated (5 h) and cell-mediated, delayed-type (24 h) hypersensitivity to schistosome egg antigens than did the other two infection groups. In an attempt to determine possible mechanisms for the reduced inflammatory responses, we also measured hepatic mRNA levels of cytokines that have been shown to influence granuloma size (IL-4, IL-10, and IFN-gamma). The mRNA levels for IL-10 were significantly lower in 5-LO-deficient mice, but SEA-stimulated spleen cells did not demonstrate a significant difference in IL-10 production between wild type and 5-LO mice. These data suggest that 5-LO plays a role in host responses to schistosomiasis via a mechanism that cannot be explained solely by changes in expression of these cytokines.
Secor
W E
WE
Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA. was4@cdc.gov
Powell
M R
MR
Morgan
J
J
Wynn
T A
TA
Funk
C D
CD
D000818:Animals; D000947:Antigens, Helminth / Q000097:blood; D001092:Arachidonate 12-Lipoxygenase / Q000172:deficiency / Q000502:physiology*; D001094:Arachidonate 5-Lipoxygenase / Q000172:deficiency / Q000502:physiology*; D002452:Cell Count; D004804:Eosinophils / Q000737:chemistry / Q000276:immunology; D006023:Glycoproteins / Q000097:blood; D006099:Granuloma / Q000209:etiology; D015801:Helminth Proteins / Q000097:blood; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000032:analysis; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008107:Liver Diseases / Q000209:etiology / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D010063:Ovum / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012552:Schistosomiasis / Q000276:immunology*; D012555:Schistosomiasis mansoni