An impact of latent toxoplasmosis reactivation on immune system and clinical dynamics in patients with mild cognitive impairment

Mild cognitive impairment (MCI) in a number of cases precedes the development of dementia. Neuroinflammation is one of the key factors in neurodegeneration pathogenesis. Chronic infections and parasitic infestations contribute significantly to neuroinflammation. It has been evident about a link between systemic inflammation, disorders of cellular and humoral immunity and MCI progression. In this context, of particular interest is a role for a common intracellular pathogen Toxoplasma gondii may be involved in MCI pathogenesis and clinical dynamics. Currently, the frequency and clinical significance of toxoplasmosis reactivation in MCI remain unknown. Given Toxoplasma gondii-related immunotropic effects, it is also relevant to investigate an association between latent toxoplasmosis reactivation, immune parameters and inflammatory mediators in MCI. The study was aimed at assessing the frequency of chronic toxoplasmosis reactivation and its associations with cell immunity, levels of main cytokines and chemokines along with clinical dynamics in MCI. For this, individuals were divided into the following groups: main group included 130 patients with MCI, and comparison group — 81 patients with subjective cognitive impairment (preMCI). The serum was tested for anti-Toxoplasma gondii IgG, IgM, and IgA antibodies using enzyme-linked immunosorbent assay, the concentration of cytokines and chemokines was determined by multiplex assay. Cell immunity was assessed using flow cytometry. The Kruskal–Wallis test was used to assess the significance of differences, followed by pairwise comparisons with Mann–Whitney test. An increased frequency of latent toxoplasmosis reactivation (positive for anti-Toxoplasma gondii IgA in combination with IgG 50 IU/mL) was observed in MCI. In MCI patients, reactivation of toxoplasmosis was associated with impaired activation of Th1-cell immunity (lower total and subset T-cell counts including CD4+CD57+ T-cells and CD8+CD57+ T-cells), as well as increased levels and activation of NK-cells. Higher anti-Toxoplasma gondii IgG level in patients was associated with elevated neuroinflammatory markers CCL4 and CCL20, and with less favorable one-year-follow-up clinical dynamics. The results suggest that reactivation of latent toxoplasmosis in MCI may be clinically relevant, and it is important to determine not only anti-Toxoplasma gondii IgG and IgM, but also IgA to detect it.