Neuroimmune-Endocrine Modulation of T-Cell Exhaustion in Central Nervous System Parasitic Diseases: Insights from Toxoplasmosis and Neurocysticercosis.

BACKGROUND: Parasitic infections of the central nervous system (CNS) represent a considerable health burden in low- and middle-income countries. During chronic disease, parasites modulate host immunity to ensure long-term persistence while limiting collateral tissue damage. A key feature of this immune remodeling is the progressive T-cell dysfunction that may culminate in T-cell exhaustion, characterized by increased expression of inhibitory receptors (TIM-3, LAG-3, KLRG1), checkpoint molecules (PD-1, PD-L1), suppressor of cytokine signaling-1 (SOCS1), and arginase-1.

SUMMARY: The relevance of the neuroimmune-endocrine (NIE) axis on the modulation of T-cell dysfunction related to parasite survival needs to be explored. This review focuses on two parasitic CNS infections: neurotoxoplasmosis induced by the intracellular protozoan Toxoplasma gondii and neurocysticercosis caused when cysticercus of the cestode Taenia solium lodges in the CNS.

KEY MESSAGES: We present updated evidence on how these phylogenetically distant pathogens exploit the NIE network, describe the physiological consequences for the host, and highlight shared and distinct mechanisms behind T-cell exhaustion. Finally, we address emerging immunotherapeutic strategies aimed at reversing exhaustion and restoring protective immunity.