Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Feb 15;212(4):617-631.
doi: 10.4049/jimmunol.2300509.

Memory-like NK Cells Are a Critical Component of Vaccine-Induced Immunity to Trypanosoma cruzi Infection

Aline L Horta  1 , Jason Gigley  2 , Marie Boutet  3 , Gregoire Lavau  3 , Louis M Weiss  1   4 , Huan Huang  1
Affiliations

Memory-like NK Cells Are a Critical Component of Vaccine-Induced Immunity to Trypanosoma cruzi Infection

Aline L Horta et al. J Immunol. .

Abstract

Chagas disease by Trypanosoma cruzi infection is a major public health issue. The available therapeutic agents have limited efficacy and significant side effects. A reliable vaccine would reduce the threat of T. cruzi infections and prevent Chagas disease. Understanding the immune response to this infection would improve vaccine design. We previously demonstrated that adoptively transferred NK cells from mice immunized with highly attenuated T. cruzi, GFP-DDDHA strain, provided potent protection in naive recipients against secondary lethal challenge with various wild-type (WT) strains. To understand the importance of NK cells in protecting mice against T. cruzi infection, we performed an in-depth characterization of NK cell phenotype, responses, and memory-like traits during acute infections due to GFP-DDDHA and WT strains and in immunized mice during a recall response to a WT lethal challenge. NK cells robustly expanded and became more mature and cytolytic during the GFP-DDDHA strain immunization. NK cells in immunized mice responded more robustly after WT lethal challenge than during an acute primary WT infection. In addition, protection by immunization with the GFP-DDDHA strain is significantly weakened in NK cell-deficient mice and did not prevent parasitemia from WT lethal challenge, indicating that NK cells with memory-like traits were a critical component for early control of WT lethal challenge. Prior T. cruzi vaccine development studies have not included studies of this rapid NK response. These findings provide insights into overcoming existing challenges in developing a safe and effective vaccine to prevent this infection.

PubMed Disclaimer

Similar articles

See all similar articles

References

    1. Narni-Mancinelli E, Ugolini S, and Vivier E. 2013. Tuning the threshold of natural killer cell responses. Curr Opin Immunol 25: 53–58. - PubMed
    1. Romee R, Schneider SE, Leong JW, Chase JM, Keppel CR, Sullivan RP, Cooper MA, and Fehniger TA. 2012. Cytokine activation induces human memory-like NK cells. Blood 120: 4751–4760. - PMC - PubMed
    1. Keppel MP, Yang L, and Cooper MA. 2013. Murine NK cell intrinsic cytokine-induced memory-like responses are maintained following homeostatic proliferation. J. Immunol 190: 4754–4762. - PMC - PubMed
    1. Paust S, Blish CA, and Reeves RK. 2017. Redefining Memory: Building the Case for Adaptive NK Cells. J Virol 91: e00169–17. - PMC - PubMed
    1. Brillantes M, and Beaulieu AM. 2020. Memory and Memory-Like NK Cell Responses to Microbial Pathogens. Front cell infect 10:102. - PMC - PubMed

Substances

LinkOut - more resources