In:
Infection and Immunity, American Society for Microbiology, Vol. 91, No. 2 ( 2023-02-16)
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.
Type of Medium:
Online Resource
ISSN:
0019-9567
,
1098-5522
DOI:
10.1128/iai.00323-22
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2023
detail.hit.zdb_id:
1483247-1
