An official website of the United States government
Abstract The evolution of host immunity occurs in the context of the microbiome, but little theory exists to predict how resistance against pathogens might be influenced by the need to tolerate and regulate commensal microbiota. We present a general model to explore the optimal investment in host immunity under conditions in which the host can, versus cannot easily distinguish among commensal versus pathogenic bacteria, and when commensal microbiota can, versus cannot protect the host against the impacts of pathogen infection. We find that a loss of immune vigilance associated with innate immunity over evolutionary time can occur due to the challenge of discriminating between pathogenic and other microbe species. Further, we find the greater the protective effect of microbiome species, acting either directly or via competition with a pathogen, or the higher the costs of immunity, the more likely the loss of immune vigilance is. Conversely, this effect can be reversed when pathogens increase host mortality. Generally, the magnitude of costs of immunity required to allow evolution of decreased immune vigilance are predicted to be lowest when microbiome and pathogen species most resemble each other (in terms of host recognition), and when immune effects on the pathogen are weak. Our model framework makes explicit the core trade-offs likely to shape the evolution of immunity in the context of microbiome/pathogen discrimination. We discuss how this informs interpretation of patterns and process in natural systems, including vulnerability to pathogen emergence.
more »
« less
This content will become publicly available on January 23, 2026
Developmental synchrony and extraordinary multiplication rates in pathogenic organisms
The multiplication rates of pathogenic organisms influence disease progression, efficacy of immunity and therapeutics, and potential for within-host evolution. Thus, accurate estimates of multiplication rates are essential for biological understanding. We recently showed that common methods for inferring multiplication rates from malaria infection data substantially overestimate true values (i.e. under simulated scenarios), providing context for extraordinarily large estimates in human malaria parasites. A key unknown is whether this bias arises specifically from malaria parasite biology or represents a broader concern. Here, we identify the potential for biased multiplication rate estimates across pathogenic organisms with different developmental biology by generalizing a within-host malaria model. We find that diverse patterns of developmental sampling bias—the change in detectability over developmental age—reliably generate overestimates of the fold change in abundance, obscuring not just true growth rates but potentially even whether populations are expanding or declining. This pattern emerges whenever synchrony—the degree to which development is synchronized across the population of pathogenic organisms comprising an infection—decays with time. Only with simulated increases in synchrony do we find noticeable underestimates of multiplication rates. Obtaining robust estimates of multiplication rates may require accounting for diverse patterns of synchrony in pathogenic organisms. This article is part of the Theo Murphy meeting issue ‘Circadian rhythms in infection and immunity’.
more »
« less
- Award ID(s):
- 2029262
- PAR ID:
- 10621003
- Publisher / Repository:
- Royal Society
- Date Published:
- Journal Name:
- Philosophical Transactions of the Royal Society B: Biological Sciences
- Volume:
- 380
- Issue:
- 1918
- ISSN:
- 0962-8436
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Buchler, Nicolas E (Ed.)ABSTRACT Infectious diseases remain a major cause of global mortality, yet basic questions concerning the relationship between within-host processes governing pathogen burden (pathogen replication, immune responses) and population-scale (epidemiological) patterns of mortality remain obscure. We use a structured literature review to leverage the extensive biomedical data generated by controlled host infections to address the epidemiological question of whether infection-induced mortality is constant, accelerating, or follows some other pattern of change and to infer the within-host mechanistic basis of this pattern. We show that across diverse lethal infection models, the risk of death increases approximately exponentially in time since infection, in a manner phenomenologically similar to the dynamics of all-cause death. We further show that this pattern of accelerating risk is consistent with multiple alternate mechanisms of pathogen growth and host-pathogen interaction, underlining the limitations of current experimental approaches to connect within-host processes to epidemiological patterns. We review critical experimental questions that our work highlights, requiring additional non-invasive data on pathogen burden throughout the course of infection.IMPORTANCEHere, we ask a simple question: what are the dynamics of pathogen-induced death? Death is a central phenotype in both biomedical and epidemiological infectious disease biology, yet very little work has attempted to link the biomedical focus on pathogen dynamics within a host and the epidemiological focus on populations of infected hosts. To systematically characterize the dynamics of death in controlled animal infections, we analyzed 209 data sets spanning diverse lethal animal infection models. Across experimental models, we find robust support for an accelerating risk of death since the time of infection, contrasting with conventional epidemiological models that assume a constant elevated risk of death. Using math models, we show that multiple processes of growth and virulence are consistent with accelerating risk of death, and we end with a discussion of critical experiments to resolve how within-host biomedical processes map onto epidemiological patterns of disease.more » « less
-
null (Ed.)A key challenge surrounding ongoing climate shifts is to identify how they alter species interactions, including those between hosts and parasites. Because transmission often occurs during critical time windows, shifts in the phenology of either taxa can alter the likelihood of interaction or the resulting pathology. We quantified how phenological synchrony between vulnerable stages of an amphibian host ( Pseudacris regilla ) and infection by a pathogenic trematode ( Ribeiroia ondatrae ) determined infection prevalence, parasite load and host pathology. By tracking hosts and parasite infection throughout development between low- and high-elevation regions (San Francisco Bay Area and the Southern Cascades (Mt Lassen)), we found that when phenological synchrony was high (Bay Area), each established parasite incurred a 33% higher probability of causing severe limb malformations relative to areas with less synchrony (Mt Lassen). As a result, hosts in the Bay Area had up to a 50% higher risk of pathology even while controlling for the mean infection load. Our results indicate that host–parasite interactions and the resulting pathology were the joint product of infection load and phenological synchrony, highlighting the sensitivity of disease outcomes to forecasted shifts in climate.more » « less
-
A key challenge surrounding ongoing climate shifts is to identify how they alter species interactions, including those between hosts and parasites. Because transmission often occurs during critical time windows, shifts in the phenology of either taxa can alter the likelihood of interaction or the resulting pathology. We quantified how phenological synchrony between vulnerable stages of an amphibian host (Pseudacris regilla) and infection by a pathogenic trematode (Ribeiroia ondatrae) determined infection prevalence, parasite load and host pathology. By tracking hosts and parasite infection throughout development between low- and high-elevation regions (San Francisco Bay Area and the Southern Cascades (Mt Lassen)), we found that when phenological synchrony was high (Bay Area), each established parasite incurred a 33% higher probability of causing severe limb malformations relative to areas with less synchrony (Mt Lassen). As a result, hosts in the Bay Area had up to a 50% higher risk of pathology even while controlling for the mean infection load. Our results indicate that host–parasite interactions and the resulting pathology were the joint product of infection load and phenological synchrony, highlighting the sensitivity of disease outcomes to forecasted shifts in climate.more » « less
-
Environmental temperature fundamentally shapes insect physiology, fitness and interactions with parasites. Differential climate warming effects on host versus parasite biology could exacerbate or inhibit parasite transmission, with far-reaching implications for pollination services, biocontrol and human health. Here, we experimentally test how controlled temperatures influence multiple components of host and parasite fitness in monarch butterflies (Danaus plexippus) and their protozoan parasitesOphryocystis elektroscirrha. Using five constant-temperature treatments spanning 18–34°C, we measured monarch development, survival, size, immune function and parasite infection status and intensity. Monarch size and survival declined sharply at the hottest temperature (34°C), as did infection probability, suggesting that extreme heat decreases both host and parasite performance. The lack of infection at 34°C was not due to greater host immunity or faster host development but could instead reflect the thermal limits of parasite invasion and within-host replication. In the context of ongoing climate change, temperature increases above current thermal maxima could reduce the fitness of both monarchs and their parasites, with lower infection rates potentially balancing negative impacts of extreme heat on future monarch abundance and distribution.more » « less
