{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Matthiesen S"],"funding":["Bundesministerium für Bildung und Forschung"],"pagination":["e0032322"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9933720"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["91(2)"],"pubmed_abstract":["Dendritic cells (DCs) belong to the first line of innate defense and come into early contact with invading pathogens, including the zoonotic bacterium Coxiella burnetii, the causative agent of Q fever. However, the pathogen-host cell interactions in C. burnetii-infected DCs, particularly the role of mechanisms of immune subversion beyond virulent phase I lipopolysaccharide (LPS), as well as the contribution of cellular self-defense strategies, are not understood. Using phase II Coxiella-infected DCs, we show that impairment of DC maturation and MHC I downregulation is caused by autocrine release and action of immunosuppressive transforming growth factor-β (TGF-β). Our study demonstrates that IFN-γ reverses TGF-β impairment of maturation/MHC I presentation in infected DCs and activates bacterial elimination, predominantly by inducing iNOS/NO. Induced NO synthesis strongly affects bacterial growth and infectivity. Moreover, our studies hint that Coxiella-infected DCs might be able to protect themselves from mitotoxic NO by switching from oxidative phosphorylation to glycolysis, thus ensuring survival in self-defense against C. burnetii. Our results provide new insights into DC subversion by Coxiella and the IFN-γ-mediated targeting of C. burnetii during early steps in the innate immune response."],"journal":["Infection and immunity"],"pubmed_title":["TGF-β/IFN-γ Antagonism in Subversion and Self-Defense of Phase II Coxiella burnetii<i>-</i>Infected Dendritic Cells."],"pmcid":["PMC9933720"],"funding_grant_id":["01KI1726C"],"pubmed_authors":["Karger A","Franzke K","Jahnke R","Christiansen B","Zaeck LM","Knittler MR","Matthiesen S","Finke S"],"additional_accession":[]},"is_claimable":false,"name":"TGF-β/IFN-γ Antagonism in Subversion and Self-Defense of Phase II Coxiella burnetii<i>-</i>Infected Dendritic Cells.","description":"Dendritic cells (DCs) belong to the first line of innate defense and come into early contact with invading pathogens, including the zoonotic bacterium Coxiella burnetii, the causative agent of Q fever. However, the pathogen-host cell interactions in C. burnetii-infected DCs, particularly the role of mechanisms of immune subversion beyond virulent phase I lipopolysaccharide (LPS), as well as the contribution of cellular self-defense strategies, are not understood. Using phase II Coxiella-infected DCs, we show that impairment of DC maturation and MHC I downregulation is caused by autocrine release and action of immunosuppressive transforming growth factor-β (TGF-β). Our study demonstrates that IFN-γ reverses TGF-β impairment of maturation/MHC I presentation in infected DCs and activates bacterial elimination, predominantly by inducing iNOS/NO. Induced NO synthesis strongly affects bacterial growth and infectivity. Moreover, our studies hint that Coxiella-infected DCs might be able to protect themselves from mitotoxic NO by switching from oxidative phosphorylation to glycolysis, thus ensuring survival in self-defense against C. burnetii. Our results provide new insights into DC subversion by Coxiella and the IFN-γ-mediated targeting of C. burnetii during early steps in the innate immune response.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2026-06-08T06:41:28.609Z","creation":"2024-12-04T07:36:00.369Z"},"accession":"S-EPMC9933720","cross_references":{"pubmed":["36688662"],"doi":["10.1128/iai.00323-22"]}}