Abstract
Innate immunity has evolved as a first line defense against invading pathogens. Cellular and humoral elements of the innate immune system detect infectious parasites, initiate inflammatory resistance reactions and finally contribute to the elimination of the invaders. Repeated attacks by pathogenic agents induce adaptive responses of the innate immune system. Typically, reapplication of pathogens provokes tolerance of the affected organism. However, also stimulatory effects of primary infections on subsequent innate immune responses have been observed. The present overview touches an undervalued aspect in the innate immune response: Its pronounced dependency on pathogen load. In addition to localization and timing of innate immune responses the pathogen dose dependency might be considered as a “fifth dimension of innate immunity”. Experimental results and literature data are presented proposing a hormetic reaction pattern of innate immune cells depending on the dose of pathogens.
Similar content being viewed by others
References
Ayres, J. S., & Schneider, D. S. (2012). Tolerance of infections. [Research Support, N.I.H., Extramural Review]. Annu Rev Immunol, 30, 271-294. doi: 10.1146/annurev-immunol-020711-075030
Baker B, Maitra U, Geng S, Li L (2014) Molecular and cellular mechanisms responsible for cellular stress and low-grade inflammation induced by a super-low dose of endotoxin. J Biol Chem 289(23):16262–16269. doi:10.1074/jbc
Biswas SK, Lopez-Collazo E (2009) Endotoxin tolerance: new mechanisms, molecules and clinical significance. Trends Immunol 30(10):475–487. doi:10.1016/j.it.2009.07.009
Calabrese EJ (2013) Hormetic mechanisms. Crit Rev Toxicol 43(7):580–606. doi:10.3109/10408444.2013.808172
Figueiredo N, Chora A, Raquel H, Pejanovic N, Pereira P, Hartleben B, Moita LF (2013) Anthracyclines induce DNA damage response-mediated protection against severe sepsis. Immunity 39(5):874–884. doi:10.1016/j.immuni.2013.08.039
Foster SL, Hargreaves DC, Medzhitov R (2007) Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 447(7147):972–978. doi:10.1038/nri2634
Ifrim DC, Quintin J, Joosten LA, Jacobs C, Jansen T, Jacobs L, Netea MG (2014) rained immunity or tolerance: opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors. Clin Vaccine Immunol 21(4):534–545. doi:10.1128/CVI.00688-13
Jamieson AM, Pasman L, Yu S, Gamradt P, Homer RJ, Decker T, Medzhitov R (2013) Role of tissue protection in lethal respiratory viral-bacterial coinfection. Science 340(6137):1230–1234. doi:10.1126/science.1233632
Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Ifrim DC, Saeed S, Netea MG (2012) Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A 109(43):17537–17542. doi:10.1073/pnas.1202870109
Lehmann K, Muller JP, Schlott B, Skroblin P, Barz D, Norgauer J, Wetzker R (2009) PI3Kgamma controls oxidative bursts in neutrophils via interactions with PKCalpha and p47phox. [Research Support, Non-U.S. Gov’t]. Biochem J 419(3):603–610. doi:10.1042/BJ20081268
Medzhitov R, Horng T (2009) Transcriptional control of the inflammatory response. Nat Rev Immunol 9(10):692–703. doi:10.1038/nri2634
Medzhitov, R., Schneider, D. S., & Soares, M. P. (2012). Disease tolerance as a defense strategy. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review]. Science, 335(6071), 936-941. doi: 10.1126/science.1214935
Mogensen TH (2009) Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev 22(2):240–273. doi:10.1128/CMR.00046-08
Morris MC, Gilliam EA, Button J, Li L (2014) Dynamic modulation of innate immune response by varying dosages of lipopolysaccharide (LPS) in human monocytic cells. J Biol Chem 289(31):21584–21590. doi:10.1074/jbc.M114.583518
Ostman A, Frijhoff J, Sandin A, Bohmer FD (2011) Regulation of protein tyrosine phosphatases by reversible oxidation. J Biochem 150(4):345–356. doi:10.1093/jb/mvr104
Quintin J, Saeed S, Martens JH, Giamarellos-Bourboulis EJ, Ifrim DC, Logie C, Netea MG (2012) Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe 12(2):223–232. doi:10.1016/j.chom.2012.06.006
Quintin J, Cheng SC, van der Meer JW, Netea MG (2014) Innate immune memory: towards a better understanding of host defense mechanisms. Curr Opin Immunol 29C:1–7. doi:10.1016/j.coi.2014.02.006
Schmidt C, Schneble N, Muller JP, Bauer R, Perino A, Marone R, Wetzker R (2013) Phosphoinositide 3-kinase gamma mediates microglial phagocytosis via lipid kinase-independent control of cAMP. Neuroscience 233:44–53. doi:10.1016/j.neuroscience.2012.12.036
Schneider DS (2011) Tracing personalized health curves during infections. PLoS Biol 9(9):e1001158. doi:10.1371/journal.pbio
Underhill DM, Goodridge H (2012) Information processing during phagocytosis. [Review]. Nat Rev Immunol 12(7):492–502. doi:10.1038/nri3244
West MA, Heagy W (2002) Endotoxin tolerance: a review. Crit Care Med 30(1 Supp):S64–S73
Willer Y, Müller B, Bumann D (2012) Intestinal inflammation responds to microbial tissue load independent of pathogen/non-pathogen discrimination. PLoS ONE 7(5):e35992. doi:10.1371/journal.pone.0035992
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Schmidt, C., Schneble, N. & Wetzker, R. The fifth dimension of innate immunity. J. Cell Commun. Signal. 8, 363–367 (2014). https://doi.org/10.1007/s12079-014-0246-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12079-014-0246-6