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

## TL;DR

This study shows that T cells and interferon signaling, through STAT1 and STAT2, help protect against brain infection and neurological symptoms caused by Brucella bacteria.

## Contribution

The study reveals the specific roles of T cells, STAT1, and STAT2 in protecting against neurobrucellosis in mice.

## Key findings

- T cells can prevent central nervous system infection by Brucella in an IFN-γ-dependent manner.
- STAT1 provides protection against brain colonization by Brucella, independent of IFN-γ signaling.
- Combined deficiency of STAT2 and IFN-γ receptor increases brain and blood bacterial burdens and neurological symptoms.

## Abstract

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.

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.

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.

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.

Neurologic complications are the most morbid manifestation of human brucellosis. Here, we show T cells and interferons limit colonization of the brain by Brucella and the development of neurobrucellosis in a manner dependent on STAT1 and STAT2.