AUTHOR=Chen Min , Yang Pei , Xin Zixuan , Chen Jiating , Zou Weihao , Zhou Lijuan , Yang Lili , Peng Jiao , Peng Hongjuan 

TITLE=Toxoplasma gondii gra5 deletion mutant protects hosts against Toxoplasma gondii infection and breast tumors

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1173379

DOI=10.3389/fimmu.2023.1173379

ISSN=1664-3224

ABSTRACT=<p><italic>Toxoplasma gondii</italic> is the causative agent of toxoplasmosis, a zoonotic disease that poses a threat to human health and a considerable loss to livestock farming. At present, clinical therapeutic drugs mainly target <italic>T. gondii</italic> tachyzoites and fail to eradicate bradyzoites. Developing a safe and effective vaccine against toxoplasmosis is urgent and important. Breast cancer has become a major public health problem and the therapeutic method needs to be further explored. Many similarities exist between the immune responses caused by <italic>T. gondii</italic> infection and the immunotherapy for cancers. <italic>T. gondii</italic> dense granule organelles secrete immunogenic dense granule proteins (GRAs). GRA5 is localized to the parasitophorous vacuole membrane in the tachyzoite stage and the cyst wall in the bradyzoite stage. We found that <italic>T. gondii</italic> ME49 <italic>gra5</italic> knockout strain (ME49Δ<italic>gra5</italic>) was avirulent and failed to form cysts but stimulated antibodies, inflammatory cytokines, and leukocytes infiltration in mice. We next investigated the protective efficacy of ME49Δ<italic>gra5</italic> vaccination against <italic>T. gondii</italic> infection and tumor development. All the immunized mice survived the challenge infection of either wild-type RH, ME49, VEG tachyzoites, or ME49 cysts. Moreover, ME49Δ<italic>gra5</italic> tachyzoite inoculation <italic>in situ</italic> attenuated the growth of murine breast tumor (4T1) in mice and prevented 4T1’s lung metastasis. ME49Δ<italic>gra5</italic> inoculation upregulated the levels of Th1 cytokines and tumor-infiltrating T cells in the tumor microenvironment and triggered anti-tumor responses by increasing the number of natural killer, B, and T cells, macrophages, and dendritic cells in the spleen. Collectively, these results suggested that ME49Δ<italic>gra5</italic> was a potent live attenuated vaccine against <italic>T. gondii</italic> infection and breast cancer.</p>