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Infection and Immunity, December 2002, p. 6715-6725, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6715-6725.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Type 1 Immunity Provides Optimal Protection against Both Mucosal and Systemic Trypanosoma cruzi Challenges

D. F. Hoft* and C. S. Eickhoff

Department of Internal Medicine, Saint Louis University Health Sciences Center, St. Louis, Missouri 63110

Received 21 February 2002/ Returned for modification 20 May 2002/ Accepted 12 September 2002

Chagas' disease results from infection with Trypanosoma cruzi, a protozoan parasite that establishes systemic intracellular infection after mucosal invasion. We hypothesized that ideal vaccines for mucosally invasive, intracellular pathogens like T. cruzi should induce mucosal type 2 immunity for optimal induction of protective secretory immunoglobulin A (IgA) and systemic type 1 immunity protective against intracellular replication. However, differential mucosal and systemic immune memory could be difficult to induce because of reciprocal inhibitory actions between type 1 and type 2 responses. To test our hypotheses, we investigated the protective effects of type 1 and type 2 biased vaccines against mucosal and systemic T. cruzi challenges. Intranasal vaccinations were given with recombinant interleukin-12 (IL-12)- and IL-4-neutralizing antibody (Ab) for type 1 immune bias, or recombinant IL-4 and gamma interferon-neutralizing Ab for type 2 immune bias. Cytokine RNA and protein studies confirmed that highly polarized memory immune responses were induced by our vaccination protocols. Survival after virulent subcutaneous T. cruzi challenge was used to assess systemic protection. Mucosal protection was assessed by measuring the relative inhibition of parasite replication in mucosal tissues early after oral T. cruzi challenge, using both PCR and quantitative culture techniques. As expected, only type 1 responses protected against systemic challenges (P < 0.01). However, contrary to our original hypothesis, type 1 responses optimally protected against mucosal challenges as well (P < 0.05). Type 1 and type 2 biased vaccines induced similar secretory IgA responses. We conclude that future vaccines for T. cruzi and possibly other mucosally invasive, intracellular pathogens should induce both mucosal and systemic type 1 immunity.

* Corresponding author. Mailing address: Division of Infectious Diseases and Immunology, Saint Louis University Health Sciences Center, 3635 Vista Ave., St. Louis, MO 63110. Phone: (314) 577-8648. Fax: (314) 771-3816. E-mail: hoftdf{at}slu.edu.

Editor: J. M. Mansfield

Infection and Immunity, December 2002, p. 6715-6725, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6715-6725.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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