A BTLA-Mediated Bait and Switch Strategy Permits Listeria Expansion in CD8α+ DCs to Promote Long-Term T Cell Responses

Listeria monocytogenes infected CD8 alpha(+) DCs in the spleen are essential for CD8(+) T cell generation. CD8 alpha(+) DCs are also necessary for Listeria expansion and dissemination within the host. The mechanisms that regulate CD8 alpha(+) DCs to allow Listeria expansion are unclear. We find that activating the B and T lymphocyte attenuator (BTLA), a coinhibitory receptor for T cells, suppresses, while blocking BTLA enhances, both the primary and memory CD8 T cell responses against Listeria. Btla(-/-) mice have lower effector and memory CD8(+) T cells while paradoxically also being more resistant to Listeria. Although bacterial entry into Btla(-/-) CD8 alpha(+) DCs is unaffected, Listeria fails to expand within these cells. BTLA signaling limits Fas/FasL-mediated suppression of Listeria expansion within CD8 alpha(+) DCs to more effectively alert adaptive immune cells. This study uncovers a BTLA-mediated strategy used by the host that permits Listeria proliferation to enable increasing T cell responses for long-term protection.