Avaliação do papel do fator de inibição da migração de macrófagos de Toxoplasma gondii (TgMIF) na infecção crônica pelo parasito

Abstract

Toxoplasma gondii is an obligate intracellular protozoan with marked tropism for the central nervous system and the ability to establish chronic infection associated with neuroinflammatory alterations. This parasite expresses a homolog of the Macrophage Migration Inhibitory Factor (TgMIF), a bioactive protein with immunomodulatory potential that remains poorly characterized. This study aimed to evaluate the role of TgMIF in the chronicity of T.gondii infection using female C57BL/6 mice infected intraperitoneally with 10⁴ tachyzoites of either the wild-type PRU strain (WT) or a TgMIF-deficient strain (ΔTgmif), the latter genetically modified by targeted gene deletion. Clinical parameters (survival, morbidity score, and weight variation) were monitored, along with brain parasite burden assessed by quantitative PCR targeting the Tg529 gene, and histopathological and neurodegenerative changes analyzed through hematoxylin-eosin and cresyl violet staining. Mice infected with the ΔTgmif strain exhibited more pronounced and sustained weight loss, significantly increased brain parasite burden (p < 0.01), and extensive inflammatory infiltrates, especially in the meninges and brain parenchyma. A lower density of Nissl bodies was also observed, indicating more severe neuronal damage. Although no statistically significant difference in survival rates was detected between groups, histological data revealed an exacerbated inflammatory profile in the absence of TgMIF, suggesting that this molecule actively participates in regulating the immune response within neural tissue. It is concluded that TgMIF may play a relevant role in modulating chronic infection by the parasite, favoring the control of neuroinflammation and contributing to the balance between parasite persistence and immunopathology. These findings open new perspectives for the investigation of TgMIF as a potential immunotherapeutic target in chronic cerebral toxoplasmosis.