Rallying the troops against infection

Immune cells must be trained to recognize and attack invading bacteria or viruses. Infected host cells achieve this in part by presenting pathogen-derived protein fragments in the context of major histocompatibility complex (MHC) class I, a cell-surface protein complex that activates cytotoxic T cells, and programs them to destroy cells displaying the target antigen.

New research from a team led by Youcun Qian at China’s Shanghai Institutes for Biological Sciences now reveals the NLRC5 protein as an important component of this process¹. NLRC5 belongs to a large family of signaling proteins called NOD-like receptors, but previous attempts to characterize its specific function have yielded contradictory results. To clarify its role, Qian and colleagues generated genetically-modified mice that do not produce this protein.

The absence of NLRC5 led to greatly reduced expression of genes encoding MHC class I proteins, impairing the immune system’s ability to recognize cell-penetrating intracellular bacteria. Specifically, NLRC5-deficient mice failed to mount an effective cytotoxic T cell response against one such bacterium, Listeria monocytogenes, resulting in extensive infection relative to control animals. The researchers also identified a partial, supporting role for NLRC5 in innate immunity, a non-specific reaction to pathogens that represents the body’s first line of defense against infection, demonstrating this protein’s far-reaching involvement in anti-pathogen response.