Abstract
Toxoplasmic encephalitis (TE), an opportunistic infection, is a severe health problem in immunocompromised patients. Previous studies have revealed that C57BL/6 mice are susceptible and BALB/c mice are resistant to TE. To investigate the mechanisms involved in the immunopathogenesis of TE in susceptible C57BL/6 and resistant BALB/c mice, both strains of mice were perorally infected with the Prugniuad (Pru) strain of Toxoplasma gondii. Our results showed that compared with BALB/c mice, C57BL/6 mice infected with T. gondii Pru strain had more severe brain histopathological damage, and higher mRNA expression levels of tachyzoite-specific surface antigen 1, bradyzoite-specific antigen 1, interferon gamma (IFNγ), interleukin (IL)-10, arginase1 (Arg1) (M2 marker), galectin (Gal)-3, Gal-9, T. gondii microneme protein 1 (TgMIC1), TgMIC4, and TgMIC6 during the course of infection by using quantitative real-time reverse transcription-polymerase chain reaction. Further analysis displayed that BALB/c mice showed higher numbers of microglial cells and higher levels of IL-1β, inducible nitric oxide synthase (iNOS) (M1 marker), and chitinase-3-like protein 3 (Ym1) (M2 marker) in the early infective stage [at day 14 or 35 post infection (p.i.)] compared with C57BL/6 mice, whereas C57BL/6 mice showed higher numbers of microglial cells and higher levels of IL-10, iNOS (M1 marker), and Ym1 (M2 marker) at days 35, 50, or 70 p.i. compared with BALB/c mice. Correlation analysis showed that significant positive correlations existed between Gal-3 and IL-4/IL-10/iNOS/Ym1 and between Gal-9 and IL-4/Ym1 in C57BL/6 mice; between Gal-3 and IFNγ/Arg1 and between Gal-9 and IFNγ/Arg1 in BALB/c mice. Together, our data demonstrated that different Gal-3 and Gal-9 expressions as well as different positive correlations were found between Gal-3 and T helper 1 (Th1)/Th2/M1/M2 cytokines or between Gal-9 and Th1/Th2/M2 cytokines in the brains of T. gondii Pru strain-infected C57BL/6 and BALB/c mice.
Highlights
Toxoplasma gondii, a pathogen of medical and veterinary importance, is an obligate intracellular protozoan parasite that has a global distribution and can infect almost any warm-blooded vertebrate [1]
The mRNA expression levels of tachyzoite-specific surface antigen 1 (SAG1) and bradyzoite-specific bradyzoite-specific antigen 1 (BAG1) in the brains of C57BL/6 and BALB/c mice infected with T. gondii Pru strain were detected by using qRT-PCR and the transcript
The BAG1 levels in the brains of C57BL/6 mice were significantly elevated at days 35 and 70 p.i., while the BAG1 level in BALB/c mice was significantly reduced at day 70 p.i
Summary
Toxoplasma gondii, a pathogen of medical and veterinary importance, is an obligate intracellular protozoan parasite that has a global distribution and can infect almost any warm-blooded vertebrate [1]. All mice lineages develop a strong T helper 1 (Th1) immune response to T. gondii infection [4], the immune response to the parasite infection in the brains can be drastically different between genetically resistant mice (e.g., BALB/c mice) and that of susceptible mice (e.g., C57BL/6 mice) [5]. It has been proposed that T. gondii utilizes innate immune cells such as macrophages to migrate to immunoprivileged sites such as the central nervous system (CNS) to establish chronic infection [7]. During T. gondii infection, Th1 cells produce cytokines such as interferon gamma (IFNγ) to activate macrophages and cytotoxic T lymphocytes, while Th2 cells secrete cytokines such as IL-4 to induce humoral type immune responses [11, 12]. IFNγ-activated microglial cells significantly upregulate iNOS and produce nitric oxide (NO), which can inhibit intracellular T. gondii replication [13]
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