Immune dysfunction in caveolin-1 null mice following infection with Trypanosoma cruzi (Tulahuen strain)

Freddy A. Medina, Alex W. Cohen, Cecilia J. de Almeida, Fnu Nagajyothi, Vicki L. Braunstein, Mauro Martins Teixeira, Herbert B. Tanowitz, Michael P. Lisanti

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

In recent years, host cell caveolae/caveolins have emerged as potentially important targets for pathogenic microorganisms; therefore, we investigated the role of caveolin-1 (Cav-1) in T. cruzi infection using Cav-1 null mice. Cav-1 null and wild type mice were infected with the virulent Tulahuen strain. The mortality was 100% in both groups, but death was slightly delayed in wild type mice. The parasitemia in the Cav-1 null mice was significantly reduced compared with wild type littermates. Histopathologic examination of the heart revealed numerous pseudocysts, myonecrosis, and marked inflammation, which was similar in both mouse groups. Real-time PCR confirmed these observations. Infection of cultured cardiac fibroblasts obtained from Cav-1 null and wild type mice revealed no differences in infectivity. Determination of serum levels of several inflammatory mediators revealed a striking reduction in IFN-γ, TNF-α and components of the nitric oxide pathway in infected Cav-1 null mice. Infection of wild type mice resulted in the expected enhancement of inflammatory mediators. The defective production of chemokines and cytokines observed in vivo is in part attributed to Cav-1 null macrophages. Despite these marked differences in the response to infection by inflammatory mediators between the two mouse strains, the final outcome was similar. These results suggest that Cav-1 may play an important role in the normal development of immune responses.

Original languageEnglish (US)
Pages (from-to)325-333
Number of pages9
JournalMicrobes and Infection
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2007

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Keywords

  • Caveolin-1
  • Inflammation
  • Trypanosoma cruzi
  • null/knockout/deficient mice

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Medina, F. A., Cohen, A. W., de Almeida, C. J., Nagajyothi, F., Braunstein, V. L., Teixeira, M. M., Tanowitz, H. B., & Lisanti, M. P. (2007). Immune dysfunction in caveolin-1 null mice following infection with Trypanosoma cruzi (Tulahuen strain). Microbes and Infection, 9(3), 325-333. https://doi.org/10.1016/j.micinf.2006.12.011