CD4 Co-Receptor Regulates Sex-Specific NK Cell Responses to Acute Toxoplasma gondii Infection

Area of Science:

• Immunology
• Infectious Diseases
• Sex Differences in Immunity

Background:

• Immunity to Toxoplasma gondii exhibits sexual dimorphism, with females experiencing worse outcomes during immune dysfunction.
• Mechanisms driving these sex differences in T. gondii immunity remain largely unknown.

Purpose of the Study:

• To investigate the impact of CD4 co-receptor deficiency on T. gondii survival and NK cell responses in a sex-specific manner.
• To elucidate the role of CD4+ T cells in sex differences in T. gondii infection.

Main Methods:

• Comparison of survival and NK cell responses (IFNγ+ NK cells) in CD4 co-receptor knockout (KO) and MHCII KO female and male mice infected with T. gondii.
• Assessment of NK cell populations and function in wild-type (WT) and genetically modified mouse models.

Main Results:

• Female CD4 co-receptor KO mice showed significantly reduced survival and fewer IFNγ+ NK cells compared to males.
• Male CD4 co-receptor KO mice exhibited similar NK cell responses to WT males.
• Mice lacking MHCII (and thus CD4+ T cells) displayed no significant sex differences in survival or NK cell responses.

Conclusions:

• CD4 co-receptor expression is crucial for optimal NK cell responses and survival in female mice during acute T. gondii infection.
• These findings reveal a previously unappreciated sexually dimorphic regulatory role of CD4 co-receptors in innate immune responses to T. gondii.