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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.<\/jats:p>","DOI":"10.1159\/000548276","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T09:17:24Z","timestamp":1765358244000},"page":"266-277","source":"Crossref","is-referenced-by-count":5,"title":["Neuroimmune-Endocrine Modulation of T-Cell Exhaustion in Central Nervous System Parasitic Diseases: Insights from Toxoplasmosis and Neurocysticercosis"],"prefix":"10.1159","volume":"32","author":[{"given":"Iv\u00e1n N.","family":"P\u00e9rez-Osorio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan A.","family":"Hern\u00e1ndez-Aceves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 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