title: Chlamydia trachomatis induces anti-inflammatory effect in human macrophages by attenuation of immune mediators in Jurkat T-cells.
abstract: The chronic course of Chlamydia trachomatis infection is subtle with no obvious unusual inflammatory change. The reason for this is not clear. The data reported here explain how macrophage usual inflammatory response switches to anti-inflammatory response during C. trachomatis infection of mixed culture of macrophages and Jurkat T-cells. We assessed the establishment of productive infection in individual or mixed cell culture models, determined the status of C. trachomatis in the cells by monitoring HSP-60:MOMP or the proportions of the estimated IFUs that shed HSP-60 or MOMP. Also, the specific time-course expression of IL-12, IL-10 and IFN-γ or IL-12R, IL-10R, and IFN-γ-R during infection of cell models was assessed. Finally, the early events in cytokine elaboration in circumstances of varying intracellular Ca²⁺ levels were determined. There was evidence of productive infection in all individual and mixed cell culture models. The shedding of HSP-60 was highest in THP-1/Jurkat mixed cell culture model. The proportions of IFU that shed HSP-60 was heightened in infected THP-1/Jurkat mixed culture model, while the proportion of IFU that shed MOMP was higher in infected macrophage/Jurkat mixed culture and infected macrophages only. There was profound early elaboration of IL-10, varying significantly from IL-12 and IFN-γ in all infected individual or mixed cell culture models except in the case of Jurkat; where all cytokine elaboration was downregulated. The receptor to IL-10 was upregulated in infected macrophage/Jurkat cells and THP-1/Jurkat cells compared with other models in which IL-12 and IFN-γ receptors were more expressed. There was no observed significant change in cytokine in any model following the impairment of intracellular Ca²⁺ except in the case of macrophage/Jurkat cell model in which IL-12 and IL-10 were upregulated in 1h or 3 h, respectively. The implication of these findings is that C. trachomatis mediates a switch from inflammatory to anti-inflammatory function in macrophages due to downregulation of the regulatory cytokine, IFN-γ in Jurkat cells, culminating in C. trachomatis chronic course.
authors.affiliation: Department of Health Sciences, University of Wisconsin, Milwaukee, WI 53211, USA. aazenabo@uwm.edu
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Azenabor
authors.forename: Jenniffer
authors.initials: J
authors.lastname: Cintrón-Cuevas
authors.forename: Heather
authors.initials: H
authors.lastname: Schmitt
authors.forename: Violet
authors.initials: V
authors.lastname: Bumah
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000276:immunology* / Q000472:pathogenicity; D002908:Chronic Disease; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D019169:Jurkat Cells; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D018834:Chaperonin 60; D016207:Cytokines; D018836:Inflammation Mediators; D018121:Receptors, Cytokine; C078167:OMPA outer membrane proteins