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Infection and Immunity, July 2004, p. 3812-3822, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.3812-3822.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Infection with Toxoplasma gondii Reduces Established and Developing Th2 Responses Induced by Nippostrongylus brasiliensis Infection

Oliver Liesenfeld,1* Ildiko R. Dunay,1 and Klaus J. Erb2

Institut für Infektionsmedizin, Abteilung für Medizinische Mikrobiologie und Infektionsimmunologie, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, 12203 Berlin,1 Zentrum für Infektionsforschung der Universität Würzburg, 97070 Würzburg, Germany2

Received 11 June 2003/ Returned for modification 19 August 2003/ Accepted 11 March 2004

Oral infection of C57BL/6 mice with 100 cysts of the protozoan parasite Toxoplasma gondii results in the development of small intestinal Th1-type immunopathology. In contrast, infection with intestinal helminths results in the development of protective Th2-type responses. We investigated whether infection with the helminth Nippostrongylus brasiliensis influences the development of T. gondii-induced Th1 responses and immunopathology in C57BL/6 mice infected with T. gondii. Prior as well as simultaneous infection of mice with N. brasiliensis did not alter the course of infection with 100 cysts of T. gondii. Coinfected mice produced high levels of interleukin-12 (IL-12) and gamma interferon (IFN-{gamma}), developed small intestinal immunopathology, and died at the same time as mice infected with T. gondii. Interestingly, local and systemic N. brasiliensis-induced Th2 responses, including IL-4 and IL-5 production by mesenteric lymph node and spleen cells and numbers of intestinal goblet cells and blood eosinophils, were markedly lower in coinfected than in N. brasiliensis-infected mice. Similar effects were seen when infection with 10 T. gondii cysts was administered following infection with N. brasiliensis. Infection of C57BL/6 mice with 10 T. gondii cysts prior to coinfection with N. brasiliensis inhibited the development of helminth-induced Th2 responses and was associated with higher and prolonged N. brasiliensis egg production. In contrast, oral administration of Toxoplasma lysate prior to N. brasiliensis infection had only a minor and short-lived effect on Th2 responses. Thus, N. brasiliensis-induced Th2 responses fail to alter T. gondii-induced Th1 responses and immunopathology, most likely because Th1 responses develop unchanged in C57BL/6 mice with a prior or simultaneous infection with N. brasiliensis. Our findings contribute to the understanding of immune regulation in coinfected animals and may assist in the design of immunotherapies for human Th1 and Th2 disorders.


* Corresponding author. Mailing address: Institut für Infektionsmedizin, Abteilung für Medizinische Mikrobiologie und Infektionsimmunologie, Charité Campus Benjamin Franklin, Hindenburgdamm 27, 12203 Berlin, Germany. Phone: 49 30 8445-3630. Fax: 49 30 8445-3830. E-mail: oliver.liesenfeld{at}charite.de.

Editor: S. H. E. Kaufmann


Infection and Immunity, July 2004, p. 3812-3822, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.3812-3822.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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