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.
Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, Trogerstr. 30, 81675 München, Germany.
Georg
G
Peschel
Lavinia
L
Kernschmidt
Christine
C
Cirl
Nina
N
Wantia
Tanja
T
Ertl
Susanne
S
Dürr
Hermann
H
Wagner
Thomas
T
Miethke
Nuria
N
Rodríguez
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000276:immunology / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000382:microbiology; D015870:Gene Expression; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013045:Species Specificity; D051720:Upstream Stimulatory Factors / Q000235:genetics / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; D007371:Interferon-gamma