TGF-ß/IFN-γ Antagonism in Subversion and Self-Defense of Phase II Coxiella burnetii-Infected Dendritic Cells.
Infect Immun
; 91(2): e0032322, 2023 02 16.
Article
em En
| MEDLINE
| ID: mdl-36688662
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-ß (TGF-ß). Our study demonstrates that IFN-γ reverses TGF-ß 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Febre Q
/
Coxiella burnetii
Limite:
Humans
Idioma:
En
Revista:
Infect Immun
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Alemanha