Comparative analysis of conventional natural killer cell responses to acute infection with Toxoplasma gondii strains of different virulence

Abstract

Abstract Toxoplasma gondii is an obligate intracellular parasitic protozoan present in 30% of humans and a significant health concern in immunocompromised people. Conventional Natural Killer Cells (cNK), members of group 1 innate lymphoid cells, are critical for early immunity to T. gondii via IFNγ production. However, little is understood about how cNK cell functionality, subpopulations, maturation and proliferation are affected by parasite infection and parasite virulence. Here we comprehensively performed this analysis with Type I virulent RH, Type II avirulent ME49 and fully attenuated Type I cps1-1 strains. In response to these three parasite strains, murine cNK cells produce IFNγ and become cytotoxic and polyfunctional (IFNγ+CD107a+) at the site of infection. In contrast to virulent RH and avirulent ME49 T. gondii strains, attenuated cps1-1 strain induced only local cNK cell responses. RH and ME49 infection significantly decreased cNK cell frequency and numbers in spleen compared with cps1-1 parasites. Responding cNK cell subsets expressing activating receptors and inhibitory receptors were similar regardless of parasite infection strain. 5 days post infection cNK cells did not proliferate, however, cellular maturation (CD27, CD11b and KLRG1) was impacted by parasite strain. cNK cell maturation was reduced after RH or ME49 infection compared with cps1-1 infection. Interestingly, KLRG1 was highly expressed on immature not mature cNK cells after RH infection. Results suggest increased parasite virulence differentially impacts cNK cell maturation during acute T. gondii infection. Different cNK cell responses could impact early immunity and susceptibility to these strains.