An Exaggerated Immune Response in Female BALB/c Mice Controls Initial Toxoplasma gondii Multiplication but Increases Mortality and Morbidity Relative to Male Mice

Abstract

Studies indicate that female mice are more susceptible to T. gondii infection, as defined by higher mortality rates in comparison to male mice. However, whether this is due to an inability to control initial parasite multiplication or due to detrimental effects of the immune system has not been determined. Therefore, the following studies were undertaken to determine the influence of sex on early parasite multiplication and the immune response during T. gondii infection and to correlate this with disease outcome. Early parasite replication was studied through applying an in vivo imaging system (IVIS) with luciferase expressing T. gondii. In parallel immunological events were studied by cytometric bead array to quantify key immunological mediators. The results confirmed the previous findings that female mice are more susceptible to acute infection, as determined by higher mortality rates and weight loss compared with males. However, conflicting with expectations, female mice had lower parasite burdens during the acute infection than male mice. Female mice also exhibited significantly increased production of Monocyte Chemoattractant Protein-1 (MCP-1), Interferon (IFN)-γ, and Tumour Necrosis Factor (TNF)-α than male mice. MCP-1 was found to be induced by T. gondii in a dose dependent manner suggesting that the observed increased levels detected in female mice was due to a host-mediated sex difference rather than due to parasite load. However, MCP-1 was not affected by physiological concentration of estrogen or testosterone, indicating that MCP-1 differences observed between the sexes in vivo are due to an as yet unidentified intermediary factor that in turn influences MCP-1 levels. These results suggest that a stronger immune response in female mice compared with male mice enhances their ability to control parasite replication but increases their morbidity and mortality.

Factors influencing tissue cyst yield in a murine model of chronic toxoplasmosis

“…Less has been done to establish if the sex of the host animal impacts the recovery of tissue cysts for infections initiated with either tachyzoites or tissue cysts. While sex based differences have been described (30)(31)(32)(33)(34)(35), the overall recovery of tissue cysts from infected from male vs female mice infected with either tachyzoites and tissue cysts showed no difference (Fig. 5A,A').…”

“…The effect of a mouse’s sex on the acute infection, its immune responses to that infection, and other aspects of the chronic infection have been investigated (30-35). Less has been done to establish if the sex of the host animal impacts the recovery of tissue cysts for infections initiated with either tachyzoites or tissue cysts.…”

“…The effect of a mouse's sex on the acute infection, its immune responses to that infection, and other aspects of the chronic infection have been investigated (30)(31)(32)(33)(34)(35).…”

Nanosphere pharmacodynamics improves safety of immunostimulatory cytokine therapy

“… 64 , 65 , 66 These data also support previous literature which suggests that female BALB/c mice produce heightened pro-inflammatory responses when compared to their male counterparts. 67

Figure 5 Histopathological assessment revealed increases in total inflammation with MTD and 10 mg IL12ns dosing groups (A–H) Tissue specimens from male (A–D) and female (E–H) experimental mice were analyzed using a thorough, tissue-specific histopathological guideline. Representative H&E images (A, E) highlight differences in portal (liver), cortical (kidney), interstitial (lung), endomyocardial (heart), and stromal (spleen) inflammation (left).

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Advances in the Immunobiology of Parasitic Diseases

“…In the case of Toxoplasmosis, Alonaizan et al [ 3 ] indicate that female mice are more susceptible to Toxoplasma gondii -infection, as defined by higher mortality rates compared to male mice. However, whether this effect is due to an inability to control initial parasite multiplication or to the detrimental impacts on the immune system has not been determined.…”