Abstract
We report that chlamydiae, which are obligate intracellular bacterial pathogens, can inhibit interferon (IFN)-gamma-inducible major histocompatibility complex (MHC) class II expression. However, the IFN-gamma-induced IFN regulatory factor-1 (IRF-1) and intercellular adhesion molecule 1 (ICAM-1) expression is not affected, suggesting that chlamydia may selectively target the IFN-gamma signaling pathways required for MHC class II expression. Chlamydial inhibition of MHC class II expression is correlated with degradation of upstream stimulatory factor (USF)-1, a constitutively and ubiquitously expressed transcription factor required for IFN-gamma induction of class II transactivator (CIITA) but not of IRF-1 and ICAM-1. CIITA is an obligate mediator of IFN-gamma-inducible MHC class II expression. Thus, diminished CIITA expression as a result of USF-1 degradation may account for the suppression of the IFN-gamma-inducible MHC class II in chlamydia-infected cells. These results reveal a novel immune evasion strategy used by the intracellular bacterial pathogen chlamydia that improves our understanding of the molecular basis of pathogenesis.
Highlights
To investigate whether chlamydia possesses the ability to evade the IFN-␥–induced immune recognition mechanism, we evaluated IFN-␥–inducible major histocompatibility complex (MHC) class II antigen expression in cells with or without chlamydial infection
To determine whether the chlamydial inhibition of HLA-DR expression occurs at the transcription or translation level, MHC class II mRNA levels were evaluated by semiquantitative RT-PCR
IFN-␥ dramatically induced the expression of DR␣, DM␣, and Ip41 mRNA in the uninfected but not the infected cells (Fig. 1 C), suggesting that chlamydial inhibition of MHC class II occurred at the transcription level
Summary
Cell samples were stained with mouse anti– HLA-DR␣ (L243; ATCC), mouse anti–human intercellular adhesion molecule (ICAM)-1 (HA58; PharMingen), or normal mouse IgG (Zymed Labs., Inc.). Primary antibody binding was detected using goat anti–mouse IgG conjugated with FITC (Caltag Labs.) and analyzed with a FACSCaliburTM equipped with CellQuest software (Becton Dickinson). Western blot assay was carried out as we previously described [24]. Mouse antibodies were used to detect Janus tyrosine kinase (JAK)-1 (J24320; Transduction Labs.) and STAT1␣ (SC-464; Santa Cruz Biotechnology), HLA-DR␣ (DA6.147; provided by Dr Peter Cresswell, Yale University; reference 27), and a chlamydial major outer membrane protein (MOMP; clone MC22, our unpublished data). Primary antibody binding was detected with horseradish peroxidase–conjugated goat anti–mouse IgG or –rabbit IgG, depending on the source of the primary antibodies, and visualized using an ECL kit (Amersham Corp.)
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