Intracerebral BCG infection impairs Th17 response and autoimmunity in the central nervous system

Abstract

Infectious agents have been demonstrated to contribute to the development of helper T cell‐mediated autoimmune diseases including multiple sclerosis (MS). We induced an autoimmune disease that affects the central nervous system (CNS), experimental autoimmune encephalomyelitis (EAE), in mice intracerebrally infected with Mycobacterium bovis strain bacille‐Calmette‐Guérin (BCG) to study the role of in situ infection induced inflammation on the clinical outcome of disease. We show that clinical and pathological signs of EAE did not develop in mice with intracerebral BCG infection. In parallel with this, we found intact myelin sheaths and decreased cellular infiltration in the spinal cord of BCG‐infected animals as compared to non‐infected EAE controls. Intracellular cytokine analysis of IFN‐γ and IL‐17 demonstrated a substantial reduction in MOG‐specific responses in both cytokines in BCG‐infected mice. However, the IFN‐γ response of non‐MOG specific, activated T cells in the CNS of BCG infected mice was equivalent, while these cells showed substantially reduced IL‐17 responses. In addition, BCG‐induced suppression of Th17 responses was maintained in IFN‐γ deficient animals. These data suggest that BCG infection‐mediated modulation of autoimmunity in the CNS is independent of IFN‐γ and is regulated via the Th17 pathway. Identification of the mechanisms that block CNS autoimmunity in situ in the nervous tissue will add to our understanding of the role of bacterial infections in CNS autoimmunity and could lead to the development of new strategies in manipulating autoimmune disease.[This research is supported by the National Institute of Health, USA R01‐NS 37570 01 awarded to Dr. Z. Fabry.]