Reduced display of tumor necrosis factor receptor I at the host cell surface supports infection with Chlamydia trachomatis.
The obligate intracellular human pathogenic bacterium Chlamydia trachomatis has evolved multiple mechanisms to circumvent the host immune system. Infected cells exhibit a profound resistance to the induction of apoptosis and down-regulate the expression of major histocompatibility complex class I and class II molecules to evade the cytotoxic effect of effector immune cells. Here we demonstrate the down-regulation of tumor necrosis factor receptor 1 (TNFR1) on the surface of infected cells. Interestingly, other members of the TNFR family such as TNFR2 and CD95 (Fas/Apo-1) were not modulated during infection, suggesting a selective mechanism underlying surface reduction of TNFR1. The observed effect was not due to reduced expression since the overall amount of TNFR1 protein was increased in infected cells. TNFR1 accumulated at the chlamydial inclusion and was shed by the infected cell into the culture supernatant. Receptor shedding depended on the infection-induced activation of the MEK-ERK pathway and the metalloproteinase TACE (TNFalpha converting enzyme). Our results point to a new function of TNFR1 modulation by C. trachomatis in controlling inflammatory signals during infection.
Paland
Nicole
N
Research Group for Molecular Infection and Tumor Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, Berlin, Germany.
Böhme
Linda
L
Gurumurthy
Rajendra Kumar
RK
Mäurer
André
A
Szczepek
Agnes J
AJ
Rudel
Thomas
T
D051722:ADAM Proteins / Q000276:immunology* / Q000378:metabolism; D000072198:ADAM17 Protein; D017209:Apoptosis / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology* / Q000378:metabolism; D002692:Chlamydia trachomatis / Q000276:immunology* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D019169:Jurkat Cells; D020930:MAP Kinase Kinase Kinases / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000276:immunology*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology* / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000276:immunology / Q000378:metabolism; D020298:U937 Cells; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D019014:fas Receptor; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human