The Journal of Immunology, Vol 159, Issue 4 1868-1875, Copyright © 1997 by American Association of Immunologists

ARTICLES

Fc epsilonRI-deficient mice infected with Schistosoma mansoni mount normal Th2-type responses while displaying enhanced liver pathology

D Jankovic, MC Kullberg, D Dombrowicz, S Barbieri, P Caspar, TA Wynn, WE Paul, AW Cheever, JP Kinet and A Sher
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

The IgE/Fc epsilonRI interaction is postulated to play an important role in resistance to helminths both at the level of anti-parasitic effector cell function and in the initiation of Th2 responses through IL-4 produced by Fc epsilonRI+ non-B, non-T (NBNT) cells. To formally evaluate the role of IgE/Fc epsilonRI signaling in the host response to helminths we studied Schistosoma mansoni infection in Fc epsilonRI knockout (KO) mice. Infected wild-type (wt) and KO animals showed comparable adult worm and tissue egg burdens, arguing against a role for Fc epsilonRI interactions in host resistance. Significantly, NBNT cells from infected KO, in contrast to wt animals, did not secrete IL-4 when stimulated with anti-IgE Ab or soluble parasite Ag. Nevertheless, serum IgE levels and Th2 cytokine production profiles were comparable in both strains of mice, demonstrating that the Ag-dependent stimulation of IL-4 secretion by NBNT cells is not essential for helminth-induced Th2 differentiation. However, when stimulated with low Ag doses, splenocytes from infected Fc epsilonRI-deficient mice produced less IL-4 in vitro than similar cultures from infected wt animals, an effect attributable to their defective NBNT cell function. Moreover, infected KO mice showed enhanced egg granuloma formation and hepatic fibrosis, revealing that the IgE/Fc epsilonRI interaction, while not essential for Th2 response development or resistance to primary infection, plays a significant role in down-regulating host pathology.

This article has been cited by other articles:

				B. Frossi, J. Rivera, E. Hirsch, and C. Pucillo Selective Activation of Fyn/PI3K and p38 MAPK Regulates IL-4 Production in BMMC under Nontoxic Stress Condition J. Immunol., February 15, 2007; 178(4): 2549 - 2555. [Abstract] [Full Text] [PDF]

				T. NARA, K. IIZUMI, H. OHMAE, O. S. SY, S. TSUBOTA, Y. INABA, A. TSUBOUCHI, M. TANABE, S. KOJIMA, and T. AOKI ANTIBODY ISOTYPE RESPONSES TO PARAMYOSIN, A VACCINE CANDIDATE FOR SCHISTOSOMIASIS, AND THEIR CORRELATIONS WITH RESISTANCE AND FIBROSIS IN PATIENTS INFECTED WITH SCHISTOSOMA JAPONICUM IN LEYTE, THE PHILIPPINES Am J Trop Med Hyg, February 1, 2007; 76(2): 384 - 391. [Abstract] [Full Text] [PDF]

				Y. Kanamaru, L. Scandiuzzi, M. Essig, C. Brochetta, C. Guerin-Marchand, Y. Tomino, R. C. Monteiro, M. Peuchmaur, and U. Blank Mast Cell-Mediated Remodeling and Fibrinolytic Activity Protect against Fatal Glomerulonephritis J. Immunol., May 1, 2006; 176(9): 5607 - 5615. [Abstract] [Full Text] [PDF]

				B. Frossi, M. De Carli, and C. Pucillo The mast cell: an antenna of the microenvironment that directs the immune response J. Leukoc. Biol., April 1, 2004; 75(4): 579 - 585. [Abstract] [Full Text] [PDF]

				A. B. Stavitsky Regulation of Granulomatous Inflammation in Experimental Models of Schistosomiasis Infect. Immun., January 1, 2004; 72(1): 1 - 12. [Full Text] [PDF]

				D. Dombrowicz, B. Quatannens, J.-P. Papin, A. Capron, and M. Capron Expression of a Functional Fc{epsilon}RI on Rat Eosinophils and Macrophages J. Immunol., August 1, 2000; 165(3): 1266 - 1271. [Abstract] [Full Text] [PDF]

				D. Jankovic, M. C. Kullberg, N. Noben-Trauth, P. Caspar, W. E. Paul, and A. Sher Single Cell Analysis Reveals That IL-4 Receptor/Stat6 Signaling Is Not Required for the In Vivo or In Vitro Development of CD4+ Lymphocytes with a Th2 Cytokine Profile J. Immunol., March 15, 2000; 164(6): 3047 - 3055. [Abstract] [Full Text] [PDF]

				P. W. Mola, I. O. Farah, T. M. Kariuki, M. Nyindo, R. E. Blanton, and C. L. King Cytokine Control of the Granulomatous Response in Schistosoma mansoni-Infected Baboons: Role of Exposure and Treatment Infect. Immun., December 1, 1999; 67(12): 6565 - 6571. [Abstract] [Full Text] [PDF]

				M. A. Montesano, D. G. Colley, G. L. Freeman Jr., and W. E. Secor Neonatal Exposure to Idiotype Induces Schistosoma mansoni Egg Antigen-Specific Cellular and Humoral Immune Responses J. Immunol., July 15, 1999; 163(2): 898 - 905. [Abstract] [Full Text] [PDF]

				K. F. Hoffmann, S. L. James, A. W. Cheever, and T. A. Wynn Studies with Double Cytokine-Deficient Mice Reveal That Highly Polarized Th1- and Th2-Type Cytokine and Antibody Responses Contribute Equally to Vaccine-Induced Immunity to Schistosoma mansoni J. Immunol., July 15, 1999; 163(2): 927 - 938. [Abstract] [Full Text] [PDF]

				M. Nyindo, T. M. Kariuki, P. W. Mola, I. O. Farah, L. Elson, R. E. Blanton, and C. L. King Role of Adult Worm Antigen-Specific Immunoglobulin E in Acquired Immunity to Schistosoma mansoni Infection in Baboons Infect. Immun., February 1, 1999; 67(2): 636 - 642. [Abstract] [Full Text] [PDF]

				K. F. Hoffmann, P. Caspar, A. W. Cheever, and T. A. Wynn IFN-{gamma}, IL-12, and TNF-{alpha} Are Required to Maintain Reduced Liver Pathology in Mice Vaccinated with Schistosoma mansoni Eggs and IL-12 J. Immunol., October 15, 1998; 161(8): 4201 - 4210. [Abstract] [Full Text] [PDF]

				D. Jankovic, A. W. Cheever, M. C. Kullberg, T. A. Wynn, G. Yap, P. Caspar, F. A. Lewis, R. Clynes, J. V. Ravetch, and A. Sher CD4+ T Cell-mediated Granulomatous Pathology in Schistosomiasis Is Downregulated by a B Cell-dependent Mechanism Requiring Fc Receptor Signaling J. Exp. Med., February 16, 1998; 187(4): 619 - 629. [Abstract] [Full Text] [PDF]

				M. A. Montesano, D. G. Colley, M. T. Willard, G. L. Freeman Jr., and W. E. Secor Idiotypes Expressed Early in Experimental Schistosoma mansoni Infections Predict Clinical Outcomes of Chronic Disease J. Exp. Med., May 6, 2002; 195(9): 1223 - 1228. [Abstract] [Full Text] [PDF]