Abstract
Linkages between human innate immune capacity, the environment in which we live, and the development of clinical tolerance versus a spectrum of disease phenotypes are a major focus of inflammatory disease research. While extensive epidemiologic evidence indicates key roles for the microbiome and other environmental factors, the underlying mechanisms that explain how these stimuli lead to a given clinical phenotype remain speculative. Here we review strategies for characterizing human cytokine production ex vivo in response to innate immune receptor stimulation with defined ligands. Human cytokine and chemokine biomarker data provides a tool to test hypotheses on the relationship between innate immune capacity in vivo and expression of current or future clinical phenotypes. The most important limitations of experimental strategies that have been used to date are reviewed. Detailed experimental protocols are provided for characterization of pattern recognition receptor (PRR)-driven stimulation with a panel of bacterial (TLR4, TLR5) and viral (TLR3, TLR7/8, RIG-I/MDA5) ligands to assess the role played by human pro-inflammatory, anti-inflammatory, Th1-like, and Th2-like responses. The importance of characterizing human innate immune phenotypes extends beyond discovery-based research to development of improved strategies for prevention or inhibition of chronic inflammatory diseases, improved design of immunization programs, and more effective cancer immunotherapy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Lemaitre B, Nicolas E, Michaut L et al (1996) The dorsoventral regulatory gene cassette spatzle/toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86(6):973–983
Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388(6640):394–397
Patin E, Hasan M, Bergstedt J et al (2018) Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors. Nat Immunol 19(3):302–314. https://doi.org/10.1038/s41590-018-0049-7
Blander JM, Longman RS, Iliev ID et al (2017) Regulation of inflammation by microbiota interactions with the host. Nat Immunol 18(8):851–860
Martinez FD (2014) The human microbiome. Early life determinant of health outcomes. Ann Am Thorac Soc 11(Suppl 1):S7–S12
Azad MB, Konya T, Maughan H et al (2013) Infant gut microbiota and the hygiene hypothesis of allergic disease: impact of household pets and siblings on microbiota composition and diversity. Allergy Asthma Clin Immunol 9(1):15
Prince BT, Mandel MJ, Nadeau K et al (2015) Gut microbiome and the development of food allergy and allergic disease. Pediatr Clin N Am 62(6):1479–1492
Proal AD, Albert PJ, Marshall TG (2013) The human microbiome and autoimmunity. Curr Opin Rheumatol 25(2):234–240
Proal AD, Albert PJ, Marshall TG (2014) Inflammatory disease and the human microbiome. Discov Med 17(95):257–265
Kuroda E, Coban C, Ishii KJ (2013) Particulate adjuvant and innate immunity: past achievements, present findings, and future prospects. Int Rev Immunol 32(2):209–220
Boraschi D, Castellano LRC, Italiani P (2017) Editorial: interaction of nanomaterials with the immune system: role in nanosafety and nanomedicine. Front Immunol 8:1688
Schultze JL, Aschenbrenner AC (2019) Systems immunology allows a new view on human dendritic cells. Semin Cell Dev Biol 86:15–23. https://doi.org/10.1016/j.semcdb.2018.02.017
Goldberg JL, Sondel PM (2015) Enhancing cancer immunotherapy via activation of innate immunity. Semin Oncol 42(4):562–572
Dolasia K, Bisht MK, Pradhan G et al (2018) TLRs/NLRs: shaping the landscape of host immunity. Int Rev Immunol 37(1):3–19
Lei-Leston AC, Murphy AG, Maloy KJ (2017) Epithelial cell inflammasomes in intestinal immunity and inflammation. Front Immunol 8:1168
Hirota JA, Knight DA (2012) Human airway epithelial cell innate immunity: relevance to asthma. Curr Opin Immunol 24(6):740–746
Castelo-Branco C, Soveral I (2014) The immune system and aging: a review. Gynecol Endocrinol 30(1):16–22
Gubbels Bupp MR (2015) Sex, the aging immune system, and chronic disease. Cell Immunol 294(2):102–110
Kollmann TR, Levy O, Montgomery RR et al (2012) Innate immune function by toll-like receptors: distinct responses in newborns and the elderly. Immunity 37(5):771–783
Wenzel SE (2012) Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 18(5):716–725
Holgate ST (2013) Immune circuits in asthma. Curr Opin Pharmacol 13(3):345–350
Campbell JD, Stinson MJ, Simons FE et al (2001) In vivo stability of human chemokine and chemokine receptor expression. Hum Immunol 62(7):668–678
Akdis M, Burgler S, Crameri R et al (2011) Interleukins, from 1 to 37, and interferon-gamma: receptors, functions, and roles in diseases. J Allergy Clin Immunol 127(3):701–721 e1-70
Thottingal TB, Stefura BP, Simons FE et al (2006) Human subjects without peanut allergy demonstrate T cell-dependent, TH2-biased, peanut-specific cytokine and chemokine responses independent of TH1 expression. J Allergy Clin Immunol 118(4):905–914
Acknowledgments
We thank the many researchers and volunteers who have participated as well as Caroline Graham for editorial assistance. This work was funded by CIHR (Canadian Institute for Health Research) operating grants, the Canada Research Chairs program, and AllerGen NCE.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Fitch, N., Marshall, S.J., Stefura, W.P., Chooniedass, R., Becker, A.B., HayGlass, K.T. (2019). Quantifying Human Innate Cytokine and Chemokine Responses Ex Vivo via Pattern Recognition Receptor Stimulation. In: Lympany, P., Jones, M. (eds) Allergy. Methods in Molecular Biology, vol 2020. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9591-2_6
Download citation
DOI: https://doi.org/10.1007/978-1-4939-9591-2_6
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-4939-9589-9
Online ISBN: 978-1-4939-9591-2
eBook Packages: Springer Protocols