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Infection and Immunity, October 2006, p. 5549-5560, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00319-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Anatomical Route of Invasion and Protective Mucosal Immunity in Trypanosoma cruzi Conjunctival Infection

O. K. Giddings,1 C. S. Eickhoff,2 T. J. Smith,3 L. A. Bryant,3 and D. F. Hoft1,2*

Department of Molecular Microbiology and Immunology,1 Department of Internal Medicine,2 Department of Comparative Medicine, St. Louis University Health Science Center, St. Louis, Missouri 631103

Received 24 February 2006/ Returned for modification 6 April 2006/ Accepted 3 July 2006

Trypanosoma cruzi is a protozoan parasite that can initiate mucosal infection after conjunctival exposure. The anatomical route of T. cruzi invasion and spread after conjunctival parasite contamination remains poorly characterized. In the present work we have identified the sites of initial invasion and replication after contaminative conjunctival challenges with T. cruzi metacyclic trypomastigotes using a combination of immunohistochemical and real-time PCR confirmatory techniques in 56 mice between 3 and 14 days after challenge. Our results demonstrate that the predominant route of infection involves drainage of parasites through the nasolacrimal duct into the nasal cavity. Initial parasite invasion occurs within the ductal and respiratory epithelia. After successive waves of intracellular replication and cell-to-cell spread, parasites drain via local lymphatic channels to lymph nodes and then disseminate through the blood to distant tissues. This model of conjunctival challenge was used to identify immune responses associated with protection against mucosal infection. Preceding mucosal infection induces mucosal immunity, resulting in at least 50-fold reductions in recoverable tissue parasite DNA in immune mice compared to controls 10 days after conjunctival challenge (P < 0.05). Antigen-specific gamma interferon production by T cells was increased at least 100-fold in cells harvested from immune mice (P < 0.05). Mucosal secretions containing T. cruzi-specific secretory immunoglobulin A harvested from immune mice were shown to protect against mucosal parasite infection (P < 0.05), demonstrating that mucosal antibodies can play a role in T. cruzi immunity. This model provides an important tool for detailed studies of mucosal immunity necessary for the development of mucosal vaccines.

* Corresponding author. Mailing address: Division of Infectious Diseases and Immunology, St. Louis University Health Science Center, 3635 Vista Ave., FDT-8N, St. Louis, MO 63110. Phone: (314) 577-8648. Fax: (314) 771 3816. E-mail: hoftdf{at}slu.edu.

Editor: J. F. Urban, Jr.

Infection and Immunity, October 2006, p. 5549-5560, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00319-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Padilla, A. M., Simpson, L. J., Tarleton, R. L. (2009). Insufficient TLR Activation Contributes to the Slow Development of CD8+ T Cell Responses in Trypanosoma cruzi Infection. J. Immunol. 183: 1245-1252 [Abstract] [Full Text]  
  • Caradonna, K., PereiraPerrin, M. (2009). Preferential Brain Homing following Intranasal Administration of Trypanosoma cruzi. Infect. Immun. 77: 1349-1356 [Abstract] [Full Text]  


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