Incomplete immunity in recovered hosts is predicted to favor more virulent pathogens upon re-infection in the population. The microbiota colonizing animals can generate a similarly long-lasting, partial immune response, allowing for infection but dampened disease severity. We tracked the evolutionary trajectories of a widespread pathogen (Pseudomonas aeruginosa), experimentally passaged through populations of nematodes immune-primed by a natural microbiota member (P. berkeleyensis). This bacterium can induce genes regulated by a mitogen-activated protein kinase (MAPK) signaling pathway effective at conferring protection against pathogen-induced death despite infection. Across host populations, this incomplete immunity selected for pathogens more than twice as likely to kill as those evolved in non-primed (i.e., naive) or immune-compromised (mutants with a knockout of the MAPK ortholog) control populations. Despite the higher virulence, pathogen molecular evolution in immune-primed hosts was slow and constrained. In comparison, evolving pathogens in immune-compromised hosts were characterized by substantial genomic differentiation and attenuated virulence. These findings directly attribute the incomplete host immunity induced from microbiota as a significant force shaping the virulence and evolutionary dynamics of novel infectious diseases.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10962313 | PMC |
| http://dx.doi.org/10.1016/j.cub.2024.02.015 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
MAPK4 inhibits the early aberrant activation of B cells in rheumatoid arthritis by promoting the IRF4-SHIP1 signaling pathway.
Cell Death Dis
January 2025
Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
The involvement of B lymphocytes in the pathogenesis of rheumatoid arthritis (RA) is well-established, with their early and aberrant activation being a crucial factor. However, the mechanisms underlying this abnormal activation in RA remain incompletely understood. In this study, we identified a significant reduction in MAPK4 expression in both RA patients and collagen-induced arthritis (CIA) mouse models, which correlates with disrupted B cell activation.
View Article and Find Full Text PDFCircadian Rhythm, Hypoxia, and Cellular Senescence: From Molecular Mechanisms to Targeted Strategies.
Eur J Pharmacol
January 2025
College of Life Science, Yangtze University, Jingzhou 434025, China. Electronic address:
Cellular senescence precipitates a decline in physiological activities and metabolic functions, often accompanied by heightened inflammatory responses, diminished immune function, and impaired tissue and organ performance. Despite extensive research, the mechanisms underpinning cellular senescence remain incompletely elucidated. Emerging evidence implicates circadian rhythm and hypoxia as pivotal factors in cellular senescence.
View Article and Find Full Text PDFExploring the mechanism and drug candidates of alveolar echinococcosis affecting liver fibrosis through analysis of existing microarray data.
Acta Trop
January 2025
Department of Department of Anesthesiology, the First Affiliated Hospital of Xinjiang Medical University, No. 137, South Liyushan Road, Xinshi District, Urumqi, Xinjiang, 830054, China; Xinjiang Perioperative Organ Protection Laboratory, No. 137, South Liyushan Road, Xinshi District, Urumqi, Xinjiang, 830054, China. Electronic address:
Echinococcosis, a zoonotic disease, significantly impacts the liver, with alveolar echinococcosis (AE) often leading to liver fibrosis and, in severe cases, cirrhosis. However, the molecular mechanisms by which AE infection promotes liver fibrosis remain incompletely understood. This study utilized bioinformatic analysis of existing microarray data to explore the shared mechanisms between AE and liver fibrosis and to identify potential therapeutic drug candidates.
View Article and Find Full Text PDFAnimal Models of Non-Respiratory, Post-Acute Sequelae of COVID-19.
Viruses
January 2025
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Post-acute sequelae of COVID-19 (PASC) are a diverse set of symptoms and syndromes driven by dysfunction of multiple organ systems that can persist for years and negatively impact the quality of life for millions of individuals. We currently lack specific therapeutics for patients with PASC, due in part to an incomplete understanding of its pathogenesis, especially for non-pulmonary sequelae. Here, we discuss three animal models that have been utilized to investigate PASC: non-human primates (NHPs), hamsters, and mice.
View Article and Find Full Text PDFImmunological Regulation of Fibrosis During Heart Failure: It Takes Two to Tango.
Biomolecules
January 2025
Heart and Vascular Institute, Pennsylvania State University Hershey Medical Center, Hershey, PA 17033, USA.
Immuno-fibrotic networks and their protein mediators, such as cytokines and chemokines, have increasingly been appreciated for their critical role in cardiac healing and fibrosis during cardiomyopathy. Immune activation, trafficking, and extravasation are tightly regulated to ensure a targeted and effective response against non-self antigens/pathogens while preserving tolerance towards self-antigens and coordinate fibrotic responses for efficient scar formation, a distinction that is severely compromised during chronic diseases. It is clear that immune cells are not only the critical regulators of post-infarct healing and scarring but are also the key players in regulating fibroblast activation during left-ventricular (LV) remodeling.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!