Chlamydophila pneumoniae downregulates MHC-class II expression by two cell type-specific mechanisms.

Chlamydophila pneumoniae was shown to prevent IFN gamma-inducible upregulation of MHC-class II molecules by secreting chlamydial protease-like activity factor (CPAF) into the cytosol of those host cells which support the complete bacterial replication cycle. CPAF acts by degrading upstream stimulatory factor 1 (USF-1). However, in cells like bone marrow-derived macrophages (BMM), which restrict chlamydial replication, we show that CPAF expression is barely detectable and the expression of USF-1 is induced upon infection with C. pneumoniae. Nevertheless, the infection still reduced base line and prevented IFN gamma-inducible MHC-class II expression. Similar results were obtained with heat-inactivated C. pneumoniae. In contrast, reduction of MHC-class II molecules was not observed in MyD88-deficient BMM. Reduction of IFN gamma-inducible MHC-class II expression by C. pneumoniae in BMM was mediated in part by the MAP-kinase p38. Infection of murine embryonic fibroblasts (MEF) with C. pneumoniae, which allow chlamydial replication, induced the expression of CPAF and decreased USF-1 and MHC-class II expression. Treatment of these cells with heat-inactivated C. pneumoniae reduced USF-1 and MHC-class II expression to a much lower extent. In summary, C. pneumoniae downregulates MHC-class II expression by two cell type-specific mechanisms which are either CPAF-independent and MyD88-dependent like in BMM or CPAF-dependent like in MEFs.     «

Chlamydophila pneumoniae was shown to prevent IFN gamma-inducible upregulation of MHC-class II molecules by secreting chlamydial protease-like activity factor (CPAF) into the cytosol of those host cells which support the complete bacterial replication cycle. CPAF acts by degrading upstream stimulatory factor 1 (USF-1). However, in cells like bone marrow-derived macrophages (BMM), which restrict chlamydial replication, we show that CPAF expression is barely detectable and the expression of USF-1...     »