T-Bet Controls Susceptibility of Mice to Coxiella burnetii Infection

Soraya Mezouar (1, 2) , Hubert Lepidi (1, 2) , Ikram Omar Osman (1, 2) , Jean-Pierre Gorvel (3) , Didier Raoult (1) , Jean-Louis Mege (4) , Yassina Bechah (5, 1)

1 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection
2 MEPHI - Microbes évolution phylogénie et infections
3 CIML - Centre d'Immunologie de Marseille - Luminy
4 APHM - Assistance Publique - Hôpitaux de Marseille
5 VITROME - Vecteurs - Infections tropicales et méditerranéennes

T-bet is a transcription factor known to initiate and coordinate the gene expression program during Th1 differentiation, which is crucial for clearance of intracellular pathogens. Q fever is a worldwide zoonosis caused by Coxiella burnetii. This bacterium is transmitted to humans by aerosol. Indeed, the inhibition of the Coxiella-specific adaptive Th1 immune response leads to persistent infection and organ injury. How deficiency of T-bet affects host infection by C. burnetii has not been investigated. Here, using mice with a deletion of the T-bet gene and an airborne mode of infection to reproduce the natural conditions of C. burnetii infection, we show that infected T-bet–/– mice were more affected than wild-type mice. The lack of T-bet leads to defective bacterial control, intense replication, persistent infection, and organ injury manifesting as an increased number of granulomas. The absence of T-bet was also associated with an impaired immune response. Indeed, the production of the immunomodulatory cytokines interleukin (IL)-6 and IL-10 was increased, whereas the expression of microbicidal genes by splenocytes was impaired. Moreover, the absence of T-bet exhibited impaired production of interferon-γ, the principal cytokine released by Th1 effector cells. Thus, our study highlights the key role of T-bet in the control of C. burnetii infection in mice and leads to a reappraisal of granulomas in the pathogenesis of Q fever disease.

Mots clés: Coxiella burnetii; T-bet; granulomas; bacteria persistence; interferon-γ

Domaines: Sciences du Vivant [q-bio]

Soraya Mezouar, Hubert Lepidi, Ikram Omar Osman, Jean-Pierre Gorvel, Didier Raoult, et al.. T-Bet Controls Susceptibility of Mice to Coxiella burnetii Infection. Frontiers in Microbiology, 2020, 11, ⟨10.3389/fmicb.2020.01546⟩. ⟨hal-02998321⟩