TY - JOUR
T1 - Interferon-γ interferes with host cell metabolism during intracellular Chlamydia trachomatis infection
AU - Shima, Kensuke
AU - Kaeding, Nadja
AU - Ogunsulire, Iretiolu Mayokun
AU - Kaufhold, Inga
AU - Klinger, Matthias
AU - Rupp, Jan
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Interferon-γ (IFN-γ) is a central mediator of host immune responses including T-cell differentiation and activation of macrophages for the control of bacterial pathogens. Anti-bacterial mechanisms of IFN-γ against the obligate intracellular bacteria Chlamydia trachomatis in epithelial cells have been intensively investigated in the past, focusing on cellular tryptophan depletion by an IFN-γ induced expression of the indoleamine 2, 3-deoxygenase (IDO). In this study, we could show that IFN-γ treatment caused a significant reduction of the host cell glycolysis that was accompanied by a reduction of glucose transporter-1 (GLUT1) and hypoxia inducible factor-1α (HIF-1α) expression. Furthermore, C. trachomatis induced enhancement of glycolytic and mitochondrial activation were significantly suppressed by IFN-γ treatment. We could further show that glucose starvation, as observed under IFN-γ treatment, was associated with an attenuated antimicrobial efficacy of doxycycline (DOX) against C. trachomatis. In conclusions, anti-chlamydial activity of IFN-γ goes beyond tryptophan depletion including interference with cellular energy metabolism resulting reduced progeny, but also impaired antimicrobial susceptibility of C. trachomatis.
AB - Interferon-γ (IFN-γ) is a central mediator of host immune responses including T-cell differentiation and activation of macrophages for the control of bacterial pathogens. Anti-bacterial mechanisms of IFN-γ against the obligate intracellular bacteria Chlamydia trachomatis in epithelial cells have been intensively investigated in the past, focusing on cellular tryptophan depletion by an IFN-γ induced expression of the indoleamine 2, 3-deoxygenase (IDO). In this study, we could show that IFN-γ treatment caused a significant reduction of the host cell glycolysis that was accompanied by a reduction of glucose transporter-1 (GLUT1) and hypoxia inducible factor-1α (HIF-1α) expression. Furthermore, C. trachomatis induced enhancement of glycolytic and mitochondrial activation were significantly suppressed by IFN-γ treatment. We could further show that glucose starvation, as observed under IFN-γ treatment, was associated with an attenuated antimicrobial efficacy of doxycycline (DOX) against C. trachomatis. In conclusions, anti-chlamydial activity of IFN-γ goes beyond tryptophan depletion including interference with cellular energy metabolism resulting reduced progeny, but also impaired antimicrobial susceptibility of C. trachomatis.
UR - http://www.scopus.com/inward/record.url?scp=85048438691&partnerID=8YFLogxK
U2 - 10.1016/j.cyto.2018.05.039
DO - 10.1016/j.cyto.2018.05.039
M3 - Journal articles
AN - SCOPUS:85048438691
SN - 1043-4666
JO - Cytokine
JF - Cytokine
ER -