Transcriptional Analysis of Murine Macrophages Infected with Different Toxoplasma Strains Identifies Novel Regulation of Host Signaling Pathways

Mariane B. Melo, Quynh P. Nguyen, Cynthia Cordeiro, Musa A. Hassan, Ninghan Yang, Renée McKell, Emily E. Rosowski, Lindsay Julien, Vincent Butty, Marie Laure Dardé, Daniel Ajzenberg, Katherine Fitzgerald, Lucy H. Young, Jeroen Saeij

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Most isolates of Toxoplasma from Europe and North America fall into one of three genetically distinct clonal lineages, the type I, II and III lineages. However, in South America these strains are rarely isolated and instead a great variety of other strains are found. T. gondii strains differ widely in a number of phenotypes in mice, such as virulence, persistence, oral infectivity, migratory capacity, induction of cytokine expression and modulation of host gene expression. The outcome of toxoplasmosis in patients is also variable and we hypothesize that, besides host and environmental factors, the genotype of the parasite strain plays a major role. The molecular basis for these differences in pathogenesis, especially in strains other than the clonal lineages, remains largely unexplored. Macrophages play an essential role in the early immune response against T. gondii and are also the cell type preferentially infected in vivo. To determine if non-canonical Toxoplasma strains have unique interactions with the host cell, we infected murine macrophages with 29 different Toxoplasma strains, representing global diversity, and used RNA-sequencing to determine host and parasite transcriptomes. We identified large differences between strains in the expression level of known parasite effectors and large chromosomal structural variation in some strains. We also identified novel strain-specifically regulated host pathways, including the regulation of the type I interferon response by some atypical strains. IFNβ production by infected cells was associated with parasite killing, independent of interferon gamma activation, and dependent on endosomal Toll-like receptors in macrophages and the cytoplasmic receptor retinoic acid-inducible gene 1 (RIG-I) in fibroblasts.

Original languageEnglish (US)
Article numbere1003779
Pages (from-to)1-17
Number of pages17
JournalPLoS Pathogens
Volume9
Issue number12
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

Toxoplasma
Parasites
Macrophages
RNA Sequence Analysis
Interferon Type I
South America
Toll-Like Receptors
Toxoplasmosis
Cytoplasmic and Nuclear Receptors
North America
Tretinoin
Transcriptome
Interferon-gamma
Virulence
Fibroblasts
Genotype
Cytokines
Phenotype
Gene Expression
Genes

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Transcriptional Analysis of Murine Macrophages Infected with Different Toxoplasma Strains Identifies Novel Regulation of Host Signaling Pathways. / Melo, Mariane B.; Nguyen, Quynh P.; Cordeiro, Cynthia; Hassan, Musa A.; Yang, Ninghan; McKell, Renée; Rosowski, Emily E.; Julien, Lindsay; Butty, Vincent; Dardé, Marie Laure; Ajzenberg, Daniel; Fitzgerald, Katherine; Young, Lucy H.; Saeij, Jeroen.

In: PLoS Pathogens, Vol. 9, No. 12, e1003779, 2013, p. 1-17.

Research output: Contribution to journalArticle

Melo, MB, Nguyen, QP, Cordeiro, C, Hassan, MA, Yang, N, McKell, R, Rosowski, EE, Julien, L, Butty, V, Dardé, ML, Ajzenberg, D, Fitzgerald, K, Young, LH & Saeij, J 2013, 'Transcriptional Analysis of Murine Macrophages Infected with Different Toxoplasma Strains Identifies Novel Regulation of Host Signaling Pathways', PLoS Pathogens, vol. 9, no. 12, e1003779, pp. 1-17. https://doi.org/10.1371/journal.ppat.1003779
Melo, Mariane B. ; Nguyen, Quynh P. ; Cordeiro, Cynthia ; Hassan, Musa A. ; Yang, Ninghan ; McKell, Renée ; Rosowski, Emily E. ; Julien, Lindsay ; Butty, Vincent ; Dardé, Marie Laure ; Ajzenberg, Daniel ; Fitzgerald, Katherine ; Young, Lucy H. ; Saeij, Jeroen. / Transcriptional Analysis of Murine Macrophages Infected with Different Toxoplasma Strains Identifies Novel Regulation of Host Signaling Pathways. In: PLoS Pathogens. 2013 ; Vol. 9, No. 12. pp. 1-17.
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