Signal Transducers and Activators of Transcription 1 (STAT1), STAT2, and T Cells Mediate Interferon-Dependent Protection Against Neurobrucellosis.

BACKGROUND

Brucellosis is a significant zoonotic disease throughout the world. Human brucellosis patients develop flu-like symptoms and focal complications including arthritis and neurobrucellosis, which is the most morbid complication of Brucella infection.

METHODS

In this study, we employed murine models to uncover the role of T-cell-mediated immunity, interferons, and signal transducers and activators of transcription (STAT) signaling in the development of neurobrucellosis caused by Brucella melitensis.

RESULTS

Through adoptive transfer experiments, we discovered that T cells are recruited to the brains of Brucella-infected mice and are able to prevent central nervous system infection in an interferon-γ (IFN-γ)-dependent manner. Transferred T cells were also able to reduce established colonization of the brain by Brucella. In addition, we found that STAT1 plays a protective role against colonization of the brain by Brucella and the progression of neurobrucellosis, and that IFN-γ signaling is not entirely essential for these protective effects. While STAT2 deficiency alone did not affect Brucella burdens, a combined deficiency of STAT2 and the IFN-γ receptor led to elevated Brucella burdens in brains and blood, and a higher likelihood of developing neurologic symptoms relative to animals lacking the IFN-γ receptor alone.

CONCLUSIONS

Our findings indicate that T cells and IFN signaling through both STAT1 and STAT2 play complex and important roles in protecting against bacterial colonization and development of neurologic symptoms following infection by Brucella.