Chlamydial IFN-γ immune evasion is linked to host infection tropism

David E. Nelson, D. Virók, Heidi Wood, Christine Roshick, Raymond M. Johnson, William M. Whitmire, Deborah D. Crane, Olivia Steele-Mortimer, Laszlo Kari, Grant McClarty, Harlan D. Caldwell

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

Chlamydiae are obligate intracellular pathogens that can exhibit a broad host range in infection tropism despite maintaining near genomic identity. Here, we have investigated the molecular basis for this unique host-pathogen relationship. We show that human and murine chlamydial infection tropism is linked to unique host and pathogen genes that have coevolved in response to host immunity. This intimate host-pathogen niche revolves around a restricted repertoire of host species-specific IFN-γ-mediated effector responses and chlamydial virulence factors capable of inhibiting these effector mechanisms. In human epithelial cells, IFN-γ induces indoleamine 2,3-dioxygenase expression that inhibits chlamydial growth by depleting host tryptophan pools. Human chlamydial strains, but not the mouse strain, avoid this response by the production of tryptophan synthase that rescues them from tryptophan starvation. Conversely, in murine epithelial cells IFN-γ induces expression of p47 GTPases, but not indoleamine 2,3-dioxygenase. One of these p47 GTPases (ligp1) was shown by small interfering RNA silencing experiments to specifically inhibit human strains, but not the mouse strain. Like human strains and their host cells, the murine strain has coevolved with its murine host by producing a large toxin possessing YopT homology, possibly to circumvent host GTPases. Collectively, our findings show chlamydial host infection tropism is determined by IFN-γ-mediated immunity.

Original languageEnglish
Pages (from-to)10658-10663
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number30
DOIs
Publication statusPublished - Jul 26 2005

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Viral Tropism
Immune Evasion
GTP Phosphohydrolases
Indoleamine-Pyrrole 2,3,-Dioxygenase
Infection
Tropism
Tryptophan
Immunity
Epithelial Cells
Tryptophan Synthase
Chlamydia
Host Specificity
Virulence Factors
Starvation
RNA Interference
Small Interfering RNA
Growth
Genes

Keywords

  • Coevolution
  • Defense
  • Immunity
  • Pathogenesis
  • Virulence factors

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Chlamydial IFN-γ immune evasion is linked to host infection tropism. / Nelson, David E.; Virók, D.; Wood, Heidi; Roshick, Christine; Johnson, Raymond M.; Whitmire, William M.; Crane, Deborah D.; Steele-Mortimer, Olivia; Kari, Laszlo; McClarty, Grant; Caldwell, Harlan D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 30, 26.07.2005, p. 10658-10663.

Research output: Contribution to journalArticle

Nelson, DE, Virók, D, Wood, H, Roshick, C, Johnson, RM, Whitmire, WM, Crane, DD, Steele-Mortimer, O, Kari, L, McClarty, G & Caldwell, HD 2005, 'Chlamydial IFN-γ immune evasion is linked to host infection tropism', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 30, pp. 10658-10663. https://doi.org/10.1073/pnas.0504198102
Nelson, David E. ; Virók, D. ; Wood, Heidi ; Roshick, Christine ; Johnson, Raymond M. ; Whitmire, William M. ; Crane, Deborah D. ; Steele-Mortimer, Olivia ; Kari, Laszlo ; McClarty, Grant ; Caldwell, Harlan D. / Chlamydial IFN-γ immune evasion is linked to host infection tropism. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 30. pp. 10658-10663.
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