Dynamics of immune memory and learning in bacterial communities
- University of Toronto, Canada
Abstract
From bacteria to humans, adaptive immune systems provide learned memories of past infections. Despite their vast biological differences, adaptive immunity shares features from microbes to vertebrates such as emergent immune diversity, long-term coexistence of hosts and pathogens, and fitness pressures from evolving pathogens and adapting hosts, yet there is no conceptual model that addresses all of these together. To this end, we propose and solve a simple phenomenological model of CRISPR-based adaptive immunity in microbes. We show that in coexisting phage and bacteria populations, immune diversity in both populations is coupled and emerges spontaneously, that bacteria track phage evolution with a context-dependent lag, and that high levels of diversity are paradoxically linked to low overall CRISPR immunity. We define average immunity, an important summary parameter predicted by our model, and use it to perform synthetic time-shift analyses on available experimental data to reveal different modalities of coevolution. Finally, immune cross-reactivity in our model leads to qualitatively different states of evolutionary dynamics, including an influenza-like traveling wave regime that resembles a similar state in models of vertebrate adaptive immunity. Our results show that CRISPR immunity provides a tractable model, both theoretically and experimentally, to understand general features of adaptive immunity.
Data availability
Source code and data is available for all main text figures on GitHub at https://github.com/mbonsma/CRISPR-dynamics-model.Source data for Figures 6E-G and 7C-D is available on GitHub at https://github.com/mbonsma/CRISPR-dynamics-model.Raw simulation data has been uploaded to Dryad: https://doi.org/10.5061/dryad.sn02v6x74.
-
Simulation data from: Dynamics of immune memory and learning in bacterial communitiesDryad Digital Repository, doi:10.5061/dryad.sn02v6x74.
Article and author information
Author details
Madeleine Bonsma-Fisher
Funding
Natural Sciences and Engineering Research Council of Canada (Vanier Canada Graduate Scholarship)
- Madeleine Bonsma-Fisher
Ministry of Colleges and Universities (Queen Elizabeth II Graduate Scholarship in Science & Technology)
- Madeleine Bonsma-Fisher
Walter C. Sumner Foundation (Walter C. Sumner Memorial Fellowship)
- Madeleine Bonsma-Fisher
Natural Sciences and Engineering Research Council of Canada (Discovery Grant RGPIN-2015)
- Sidhartha Goyal
Natural Sciences and Engineering Research Council of Canada (Discovery Grant and RGPIN-2021)
- Sidhartha Goyal
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Bonsma-Fisher & Goyal
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 930
- views
-
- 210
- downloads
-
- 1
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Dynamics of immune memory and learning in bacterial communities
eLife 12:e81692.
https://doi.org/10.7554/eLife.81692
Further reading
-
- Physics of Living Systems
Chromosome structure is complex, and many aspects of chromosome organization are still not understood. Measuring the stiffness of chromosomes offers valuable insight into their structural properties. In this study, we analyzed the stiffness of chromosomes from metaphase I (MI) and metaphase II (MII) oocytes. Our results revealed a tenfold increase in stiffness (Young’s modulus) of MI chromosomes compared to somatic chromosomes. Furthermore, the stiffness of MII chromosomes was found to be lower than that of MI chromosomes. We examined the role of meiosis-specific cohesin complexes in regulating chromosome stiffness. Surprisingly, the stiffness of chromosomes from three meiosis-specific cohesin mutants did not significantly differ from that of wild-type chromosomes, indicating that these cohesins may not be primary determinants of chromosome stiffness. Additionally, our findings revealed an age-related increase of chromosome stiffness for MI oocytes. Since aging is associated with elevated levels of DNA damage, we investigated the impact of etoposide-induced DNA damage on chromosome stiffness and found that it led to a reduction in stiffness in MI oocytes. Overall, our study underscores the dynamic and cyclical nature of chromosome stiffness, modulated by both the cell cycle and age-related factors.
-
- Cancer Biology
- Physics of Living Systems
The tumor stroma consists mainly of extracellular matrix, fibroblasts, immune cells, and vasculature. Its structure and functions are altered during malignancy: tumor cells transform fibroblasts into cancer-associated fibroblasts, which exhibit immunosuppressive activities on which growth and metastasis depend. These include exclusion of immune cells from the tumor nest, cancer progression, and inhibition of T-cell-based immunotherapy. To understand these complex interactions, we measure the density of different cell types in the stroma using immunohistochemistry techniques on tumor samples from lung cancer patients. We incorporate these data into a minimal dynamical system, explore the variety of outcomes, and finally establish a spatio-temporal model that explains the cell distribution. We reproduce that cancer-associated fibroblasts act as a barrier to tumor expansion, but also reduce the efficiency of the immune response. Our conclusion is that the final outcome depends on the parameter values for each patient and leads to either tumor invasion, persistence, or eradication as a result of the interplay between cancer cell growth, T-cell cytotoxicity, and fibroblast activity. However, despite the existence of a wide range of scenarios, distinct trajectories, and patterns allow quantitative predictions that may help in the selection of new therapies and personalized protocols.
