Suppressor of cytokine signalling protein SOCS1 and UBP43 regulate the expression of type I interferon-stimulated genes in human microvascular endothelial cells infected with Rickettsia conorii

• DOI: 10.1099/jmm.0.054502-0
• Publication Date: 2013-04-05T04:29:13Z
• Authors: Punsiri M. Colonne; Abha Sahni; Sanjeev K. Sahni
• Keywords: Rickettsia conorii; STAT1; IRF1

Rickettsia conorii, the causative agent of Mediterranean spotted fever, preferentially infects human microvascular endothelium and activates pro-inflammatory innate immune responses as evidenced by enhanced expression secretion cytokines chemokines. Our recent studies reveal that endothelial cells (HMECs) infected with R. conorii also launch 'antiviral' host defence mechanisms typically governed type I interferons. To summarize, HMECs secrete IFN-β to activate STAT1 in an autocrine/paracrine manner display increased IFN-stimulated genes, for example ISG15, which turn interfere intracellular replication rickettsiae. We now present evidence UBP43 SOCS1, known negative regulators JAK/STAT signalling, are induced conorii-infected HMECs, but not SOCS1 functions negatively regulate activation. Interestingly, induction is almost completely abolished presence IFN-β-neutralizing antibody, implicating important role a feedback inhibitor IFN-β-mediated In contrast, only partially affected neutralization, potential involvement as-yet-unidentified IFN-independent mechanism(s) during infection. A number including OAS1, MX1, IRF1, IRF9 TAP1 IFN-β-dependent manner, whereas GBP1 remains unaffected neutralization. Increased phosphorylation subjected knockdown led transcriptional activation MX1 GBP1, confirming regulatory UBP43. Although were IFN-β, siRNA-mediated silencing or did significantly affect their Expression ISG15 was, however, transfected siRNA SOCS1. Thus, unique patterns UBP43, genes represent pathogen-specific underlying signalling pathogenesis fever group rickettsiosis.