An integrative systems biology view of host-pathogen interactions: The regulation of immunity and homeostasis is concomitant, flexible, and smart

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• dc.contributor.author Grossman, Zvi
• dc.contributor.author Meyerhans, Andreas
• dc.contributor.author Bocharov, Gennady A.
• dc.date.accessioned 2023-03-02T07:05:34Z
• dc.date.available 2023-03-02T07:05:34Z
• dc.date.issued 2023
• dc.description.abstract The systemic bio-organization of humans and other mammals is essentially "preprogrammed", and the basic interacting units, the cells, can be crudely mapped into discrete sets of developmental lineages and maturation states. Over several decades, however, and focusing on the immune system, we and others invoked evidence - now overwhelming - suggesting dynamic acquisition of cellular properties and functions, through tuning, re-networking, chromatin remodeling, and adaptive differentiation. The genetically encoded "algorithms" that govern the integration of signals and the computation of new states are not fully understood but are believed to be "smart", designed to enable the cells and the system to discriminate meaningful perturbations from each other and from "noise". Cellular sensory and response properties are shaped in part by recurring temporal patterns, or features, of the signaling environment. We compared this phenomenon to associative brain learning. We proposed that interactive cell learning is subject to selective pressures geared to performance, allowing the response of immune cells to injury or infection to be progressively coordinated with that of other cell types across tissues and organs. This in turn is comparable to supervised brain learning. Guided by feedback from both the tissue itself and the neural system, resident or recruited antigen-specific and innate immune cells can eradicate a pathogen while simultaneously sustaining functional homeostasis. As informative memories of immune responses are imprinted both systemically and within the targeted tissues, it is desirable to enhance tissue preparedness by incorporating attenuated-pathogen vaccines and informed choice of tissue-centered immunomodulators in vaccination schemes. Fortunately, much of the "training" that a living system requires to survive and function in the face of disturbances from outside or within is already incorporated into its design, so it does not need to deep-learn how to face a new challenge each time from scratch. Instead, the system learns from experience how to efficiently select a built-in strategy, or a combination of those, and can then use tuning to refine its organization and responses. Efforts to identify and therapeutically augment such strategies can take advantage of existing integrative modeling approaches. One recently explored strategy is boosting the flux of uninfected cells into and throughout an infected tissue to rinse and replace the infected cells.
• dc.description.sponsorship We thank Paula Cebollada Rica for artwork. AM was supported by “la Caixa” Foundation under the project code HR17-00199, the Spanish Ministry of Science and Innovation grant no. PID2019-106323RB-I00 AEI//10.13039/501100011033, and “Unidad de Excelencia María de Maeztu”, funded by the MCIN and the AEI (DOI: 10.13039/501100011033) Ref: CEX2018-000792-M. GB and AM were supported by the Russian Science Foundation (RSF grant no. 18-11-00171).
• dc.format.mimetype application/pdf
• dc.identifier.citation Grossman Z, Meyerhans A, Bocharov G. An integrative systems biology view of host-pathogen interactions: The regulation of immunity and homeostasis is concomitant, flexible, and smart. Front Immunol. 2023 Jan 24;13:1061290. DOI: 10.3389/fimmu.2022.1061290
• dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2022.1061290
• dc.identifier.issn 1664-3224
• dc.identifier.uri http://hdl.handle.net/10230/56008
• dc.language.iso eng
• dc.publisher Frontiers
• dc.relation.ispartof Front Immunol. 2023 Jan 24;13:1061290
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-106323RB-I00
• dc.rights © 2023 Grossman, Meyerhans and Bocharov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Adaptive differentiation
• dc.subject.keyword Cellular and cell population learning
• dc.subject.keyword Context discrimination
• dc.subject.keyword Functional homeostasis
• dc.subject.keyword Rinse and replace
• dc.subject.keyword Smart surveillance
• dc.subject.keyword Systems immunology
• dc.subject.keyword Tuning
• dc.title An integrative systems biology view of host-pathogen interactions: The regulation of immunity and homeostasis is concomitant, flexible, and smart
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion