Blockade of macrophage migration inhibitory factor (MIF) in Schistosoma japonicum-infected mice results in an increased adult worm burden and reduced fecundity.
Macrophage migration inhibitory factor (MIF), a cytokine produced by many cell types, modulates cellular and humoral immune responses. In schistosomiasis, ova in the portal circulation induce a delayed type hypersensitivity (DTH) that results in formation of hepatic granulomas (HG) which secrete MIF activity. Therefore, we hypothesized that endogenous MIF modulates immune responses in schistosomiasis. To test this hypothesis, Schistosoma japonicum-infected mice were injected with rabbit IgG or neutralizing rabbit IgG antibody to MIF 4.5-6.5 week post infection when HG form and female worms are laying eggs. Compared with controls, 6.5-7-week post-infection, antibody-treated mice had 1.7-3 times as many adult worms and half as many ova per worm pair in their livers. In contrast, antibody introduced before infection or 6-8 week post infection did not affect worm burden or fecundity. Thus, for the first time there is evidence that 4.5-6 week post-infection endogenous MIF somehow mediates reduction of adult worm burden and promotes fecundity. Splenocytes and HG cells from antibody-treated mice showed reduced intracellular expression of TNFalpha and/or IL-10. We hypothesize that endogenous MIF enhances adult worm attrition by up-regulating innate and adaptive immune responses by increasing expression of MHC-II, co-stimulatory, adhesion, receptor and cytokine molecules, and promotes fecundity by up-regulating TNFalpha expression.
Stavitsky
Abram B
AB
Department of Molecular Biology and Microbiology and Center for Global Health and Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4960, USA. abs7@po.cwru.edu
Metz
Christine
C
Liu
Shifan
S
Xianli
Jia
J
Bucala
Richard
R
D000818:Animals; D000947:Antigens, Helminth; D005260:Female; D005298:Fertility; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006968:Hypersensitivity, Delayed; D019746:Intramolecular Oxidoreductases; D008099:Liver / Q000276:immunology / Q000469:parasitology; D008263:Macrophage Migration-Inhibitory Factors; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D012549:Schistosoma japonicum / Q000276:immunology / Q000502:physiology; D012554:Schistosomiasis japonica / Q000276:immunology* / Q000469:parasitology
D000947:Antigens, Helminth; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; D011506:Proteins; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse