Abstract
Immunological memory is a fundamental feature of the adaptive immune system that protects the host from recurrent infections from pathogens. Natural killer (NK) cells are a predominant member of the innate immune system that lack clonotypic receptors, which are essential for memory formation. However, evidence demonstrates that a unique subpopulation of NK cells develops adaptive-like features using germline-encoded receptors. Recent studies have shown that infection of cytomegalovirus (CMV) leads to clonal expansion of NKG2C+ and Ly49H+ NK cells, in humans and mouse, respectively. These activation receptors have the capability to recognize CMV-encoded proteins and facilitate a recall response upon reinfection. Although NK cells do not rearrange genes encoding their activating receptors as seen in B and T cells, they possess a selective process to generate memory features and a long-lived progeny. Here, we describe an established in vivo protocol for infecting mice with mouse cytomegalovirus (MCMV) to study an adaptive NK cell response.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S (2008) Functions of natural killer cells. Nat Immunol 9:503–510
Zitvogel L, Terme M, Borg C, Trinchieri G (2006) Dendritic cell-NK cell cross-talk: regulation and physiopathology. Curr Top Microbiol Immunol 298:157–174
Abel AM, Yang C, Thakar MS, Malarkannan S (2018) Natural killer cells: development, maturation, and clinical utilization. Front Immunol 9:1869
O’Leary JG, Goodarzi M, Drayton DL, von Andrian UH (2006) T cell- and B cell-independent adaptive immunity mediated by natural killer cells. Nat Immunol 7:507–516
Sun JC, Beilke JN, Lanier LL (2009) Adaptive immune features of natural killer cells. Nature 457:557–561
Paust S, Senman B, von Andrian UH (2010) Adaptive immune responses mediated by natural killer cells. Immunol Rev 235:286–296
Brillantes M, Beaulieu AM (2020) Memory and memory-like NK cell responses to microbial pathogens. Front Cell Infect Microbiol 10:102
Brown MG, Dokun AO, Heusel JW, Smith HR, Beckman DL, Blattenberger EA, Dubbelde CE, Stone LR, Scalzo AA, Yokoyama WM (2001) Vital involvement of a natural killer cell activation receptor in resistance to viral infection. Science 292:934–937
Smith HR, Heusel JW, Mehta IK, Kim S, Dorner BG, Naidenko OV, Iizuka K, Furukawa H, Beckman DL, Pingel JT, Scalzo AA, Fremont DH, Yokoyama WM (2002) Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Proc Natl Acad Sci U S A 99:8826–8831
Cheng TP, French AR, Plougastel BF, Pingel JT, Orihuela MM, Buller ML, Yokoyama WM (2008) Ly49h is necessary for genetic resistance to murine cytomegalovirus. Immunogenetics 60:565–573
Sun JC, Madera S, Bezman NA, Beilke JN, Kaplan MH, Lanier LL (2012) Proinflammatory cytokine signaling required for the generation of natural killer cell memory. J Exp Med 209:947–954
Sun JC, Lopez-Verges S, Kim CC, DeRisi JL, Lanier LL (2011) NK cells and immune “memory”. J Immunol 186:1891–1897
Hanson LK, Slater JS, Karabekian Z, Virgin HW 4th, Biron CA, Ruzek MC, van Rooijen N, Ciavarra RP, Stenberg RM, Campbell AE (1999) Replication of murine cytomegalovirus in differentiated macrophages as a determinant of viral pathogenesis. J Virol 73:5970–5980
Ramakrishnan MA (2016) Determination of 50% endpoint titer using a simple formula. World J Virol 5:85–86
Hashemi E, Mei A, Wang D, Khalil MA, Malarkannan S (2021) Methods for isolating and defining single-cell transcriptomes of tissue-resident human NK cells. Methods 6(12):e05810
Wang D, Burns R, Khalil M, Mei A, Hashemi EA, Malarkannan S (2021) Methods to analyze the developmental of human primary NK cells using Monocle and SCENIC analyses. Methods Mol Biol
Acknowledgments
We dedicate this work to our inspiring colleague Dr. Mathew Riese MD, Ph.D., who passed away young. This work was supported in part by NIH R01 AI102893; NCI R01 CA179363 (S.M.); and R01 AI132414 (S.S.T.); HRHM Program of MACC Fund (S.M.), Nicholas Family Foundation (S.M.); Gardetto Family (S.M.); MCW-Cancer Center-Large Seed Grant (S.M.); MACC Fund (S.M.); Ann’s Hope Melanoma Foundation (S.M.); and Advancing Healthier Wisconsin (S.M.).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Khalil, M. et al. (2022). Method to Study Adaptive NK Cells Following MCMV Infections. In: Shimasaki, N. (eds) Natural Killer (NK) Cells. Methods in Molecular Biology, vol 2463. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2160-8_14
Download citation
DOI: https://doi.org/10.1007/978-1-0716-2160-8_14
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-2159-2
Online ISBN: 978-1-0716-2160-8
eBook Packages: Springer Protocols