A transmembrane domain-containing surface protein from Toxoplasma gondii augments replication in activated immune cells and establishment of a chronic infection

Angela M. Pollard, Sini Skariah, Dana G. Mordue, Laura J. Knoll

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Toxoplasma gondii mutants identified as defective in the establishment of chronic infection were screened to isolate those specifically impaired in their ability to replicate within activated macrophages. One of the identified mutants contains an insertion in the hypothetical gene TGME49-111670. Genetic complementation restores the ability of the mutant to replicate in immune cells and produce cysts in the brains of mice. While the mutant is more sensitive to nitric oxide than is its parental strain, it is not defective in its ability to suppress nitric oxide. The disrupted protein has no significant homology to proteins with known functions, but is predicted to have one transmembrane domain. Immunofluorescence shows the protein on the parasite surface, even in activated macrophages, colocalizing with a tachyzoite surface antigen, SAG1, and oriented with its C-terminal end external. Western analysis reveals that the protein is downregulated in bradyzoites. Despite the tachyzoite specificity of this protein, mice infected with the mutant succumb to acute infection similarly to those infected with the parent strain. Serum samples from mice with chronic T. gondii infection react to a polypeptide from TGME49-11670, indicating that the protein is seen by the immune system during infection. This study is the first to characterize a T. gondii surface protein that contains a transmembrane domain and show that the protein contributes to parasite replication in activated immune cells and the establishment of chronic infection.

Original languageEnglish
Pages (from-to)3731-3739
Number of pages9
JournalInfection and Immunity
Volume77
Issue number9
DOIs
Publication statusPublished - 1 Sep 2009
Externally publishedYes

Fingerprint

Toxoplasma
Membrane Proteins
Infection
Proteins
Nitric Oxide
Parasites
Macrophages
Toxoplasmosis
Surface Antigens
Fluorescent Antibody Technique
Cysts
Immune System
Down-Regulation
Peptides
Brain
Serum
Genes

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

A transmembrane domain-containing surface protein from Toxoplasma gondii augments replication in activated immune cells and establishment of a chronic infection. / Pollard, Angela M.; Skariah, Sini; Mordue, Dana G.; Knoll, Laura J.

In: Infection and Immunity, Vol. 77, No. 9, 01.09.2009, p. 3731-3739.

Research output: Contribution to journalArticle

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