On the control of acute rodent malaria infections by innate immunity

Does specific immunity, innate immunity or resource (red blood cell) limitation control the first peak of the blood-stage parasite in acute rodent malaria infections? Since mice deficient in specific immunity exhibit similar initial dynamics as wild-type mice it is generally viewed that the initial control of parasite is due to either limitation of resources (RBC) or innate immune responses. There are conflicting views on the roles of these two mechanisms as there is experimental evidence supporting both these hypotheses. While mathematical models based on RBC limitation are capable of describing the dynamics of primary infections, it was not clear whether a model incorporating the key features of innate immunity would be able to do the same. We examine the conditions under which a model incorporating parasite and innate immunity can describe data from acute <i>Plasmodium chabaudi</i> infections in mice. We find that innate immune response must decay slowly if the parasite density is to fall rather than equilibrate. Further, we show that within this framework the differences in the dynamics of two parasite strains are best ascribed to differences in susceptibility to innate immunity, rather than differences in the strains' growth rates or their propensity to elicit innate immunity. We suggest that further work is required to determine if innate immunity or resource limitation control acute malaria infections in mice

Competitive release of drug resistance following drug treatment of mixed Plasmodium chabaudi infections

BACKGROUND: Malaria infections are often genetically diverse, potentially leading to competition between co-infecting strains. Such competition is of key importance in the spread of drug resistance. METHODS: The effects of drug treatment on within-host competition were studied using the rodent malaria Plasmodium chabaudi. Mice were infected simultaneously with a drug-resistant and a drug-sensitive clone and were then either drug-treated or left untreated. Transmission was assessed by feeding mice to Anopheles stephensi mosquitoes. RESULTS: In the absence of drugs, the sensitive clone competitively suppressed the resistant clone; this resulted in lower asexual parasite densities and also reduced transmission to the mosquito vector. Drug treatment, however, allowed the resistant clone to fill the ecological space emptied by the removal of the sensitive clone, allowing it to transmit as well as it would have done in the absence of competition. CONCLUSION: These results show that under drug pressure, resistant strains can have two advantages: (1) they survive better than sensitive strains and (2) they can exploit the opportunities presented by the removal of their competitors. When mixed infections are common, such effects could increase the spread of drug resistance

Transmission stage investment of malaria parasites in response to in-host competition

Conspecific competition occurs in a multitude of organisms, particularly in parasites, where several clones are commonly sharing limited resources inside their host. In theory, increased or decreased transmission investment might maximize parasite fitness in the face of competition, but, to our knowledge, this has not been tested experimentally. We developed and used a clone-specific, stage-specific, quantitative PCR protocol to quantify Plasmodium chabaudi replication and transmission stage densities in mixed-clone infections. We co-infected mice from two strains with an avirulent and virulent parasite clone and found competitive suppression of in-host (blood-stage) parasite densities and generally corresponding reductions in transmission stage production, with the virulent clone obtaining overall competitive superiority. In response to competitive suppression, there was little evidence of any alteration in transmission stage investment, apart from a small reduction by one of the two clones in one of the two host strains. This alteration did not result in a competitive advantage, although it might have reduced the disadvantage. This study supports much of the current literature, which predicts that conspecific in-host competition will result in a competitive advantage and positive selection for virulent clones and thus the evolution of higher virulence

Phytochemical changes in milkweed induced by elevated CO2 alter wing morphology but not toxin sequestration in monarch butterflies

Environmental change has the potential to influence trophic interactions by altering the defensive phenotype of prey.Here, we examine the effects of a pervasive environmental change driver, elevated atmospheric concentrations of CO2 (eCO2), on toxin sequestration and flight morphology of a specialist herbivore.We fed monarch butterfly larvae, Danaus plexippus, foliage from four milkweed, Asclepias, species of varying chemical defence profiles grown under either ambient or eCO2. We also infected a subset of these herbivores with a protozoan parasite, Ophryocystis elektroscirrha, to understand how infection and environmental change combine to alter herbivore defences. We measured changes in phytochemistry induced by eCO2 and assessed cardenolide, toxic steroid, sequestration and wing morphology of butterflies.Monarchs compensated for lower plant cardenolide concentrations under eCO2 by increasing cardenolide sequestration rate, maintaining similar cardenolide composition and concentrations in their wings under both CO2 treatments. We suggest that these increases in sequestration rate are a by‐product of compensatory feeding aimed at maintaining a nutritional target in response to declining dietary quality under eCO2.Monarch wings were more suitable for sustained flight (more elongated) when reared on plants grown under eCO2 or when reared on Asclepias syriaca or Asclepias incarnata rather than on Asclepias curassavica or Asclepias speciosa. Parasite infection engendered wings less suitable for sustained flight (wings became rounder) on three of four milkweed species. Wing loading (associated with powered flight) was higher on A. syriaca than on other milkweeds, whereas wing density was lower on A. curassavica. Monarchs that fed on high cardenolide milkweed developed rounder, thinner wings, which are less efficient at gliding flight.Ingesting foliage from milkweed high in cardenolides may provide protection from enemies through sequestration yet come at a cost to monarchs manifested as lower quality flight phenotypes: rounder, thinner wings with lower wing loading values.Small changes in morphology may have important consequences for enemy evasion and migration success in many animals. Energetic costs associated with alterations in defence and morphology may, therefore, have important consequences for trophic interactions in a changing world.A plain language summary is available for this article.Plain Language SummaryPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148239/1/fec13270-sup-0006-TableS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148239/2/fec13270-sup-0003-FigS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148239/3/fec13270-sup-0004-FigS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148239/4/fec13270-sup-0002-FigS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148239/5/fec13270-sup-0008-TableS4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148239/6/fec13270-sup-0005-TableS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148239/7/fec13270-sup-0009-AppendixS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148239/8/fec13270_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148239/9/fec13270-sup-0001-Summary.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148239/10/fec13270.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148239/11/fec13270-sup-0007-TableS3.pd

The role of immune-mediated apparent competition in genetically diverse malaria infections

Competitive interactions between coinfecting genotypes of the same pathogen can impose selection on virulence, but the direction of this selection depends on the mechanisms behind the interactions. Here, we investigate how host immune responses contribute to competition between clones in mixed infections of the rodent malaria parasite Plasmodium chabaudi. We studied single and mixed infections of a virulent and an avirulent clone and compared the extent of competition in immunodeficient and immunocompetent mice (nude mice and T cellndashreconstituted nude mice, respectively). In immunocompetent mice, the avirulent clone suffered more from competition than did the virulent clone. The competitive suppression of the avirulent clone was alleviated in immunodeficient mice. Moreover, the relative density of the avirulent clone in mixed infections was higher in immunodeficient than in immunocompetent mice. We conclude that immune-mediated interactions contributed to competitive suppression of the avirulent clone, although other mechanisms, presumably competition for resources such as red blood cells, must also be important. Because only the avirulent clone suffered from immune-mediated competition, this mechanism should contribute to selection for increased virulence in mixed infections in this host-parasite system. As far as we are aware, this is the first direct experimental evidence of immune-mediated apparent competition in any host-parasite system

Behavioural resistance against a protozoan parasite in the monarch butterfly

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89483/1/j.1365-2656.2011.01901.x.pd

Feature learning for information-extreme classifier

The feature learning algorithm for information-extreme classifier by clustering of Fast Retina Keypoint binary descriptor, calculated for local features, and usage of spatial pyramid kernel for increasing noise immunity and informativeness of feature representation are considered. Proposed a method of parameters optimization for feature extractor and decision rules based on multi-level coarse features coding using information criterion and population-based search algorithm

Behavioral Immunity in Insects

Parasites can dramatically reduce the fitness of their hosts, and natural selection should favor defense mechanisms that can protect hosts against disease. Much work has focused on understanding genetic and physiological immunity against parasites, but hosts can also use behaviors to avoid infection, reduce parasite growth or alleviate disease symptoms. It is increasingly recognized that such behaviors are common in insects, providing strong protection against parasites and parasitoids. We review the current evidence for behavioral immunity in insects, present a framework for investigating such behavior, and emphasize that behavioral immunity may act through indirect rather than direct fitness benefits. We also discuss the implications for host-parasite co-evolution, local adaptation, and the evolution of non-behavioral physiological immune systems. Finally, we argue that the study of behavioral immunity in insects has much to offer for investigations in vertebrates, in which this topic has traditionally been studied

Demystifying Monarch Butterfly Migration

Every fall, millions of North American monarch butterflies undergo a stunning long-distance migration to reach their overwintering grounds in Mexico. Migration allows the butterflies to escape freezing temperatures and dying host plants, and reduces infections with a virulent parasite. We discuss the multigenerational migration journey and its evolutionary history, and highlight the navigational mechanisms of migratory monarchs. Monarchs use a bidirectional time-compensated sun compass for orientation, which is based on a time-compensating circadian clock that resides in the antennae, and which has a distinctive molecular mechanism. Migrants can also use a light-dependent inclination magnetic compass for orientation under overcast conditions. Additional environmental features, e.g., atmospheric conditions, geologic barriers, and social interactions, likely augment navigation. The publication of the monarch genome and the development of gene-editing strategies have enabled the dissection of the genetic and neurobiological basis of the migration. The monarch butterfly has emerged as an excellent system to study the ecological, neural, and genetic basis of long-distance animal migration

Effects of the parasite, Ophryocystis elektroscirrha, on wing characteristics important for migration in the monarch butterfly

There is mounting evidence that the longterm declines of overwintering monarchs in Mexico are exacerbated by losses during the fall migratory journey. Infection with the protozoan, Ophryocystis elektroscirrha (OE), is known to negatively impact migration success. Here we examine how infections affect specific wing traits of monarchs that are important for migratory success. We used a collection of infected and uninfected monarchs reared under identical conditions, and from the (deceased) specimens, measured wing area (larger monarchs are known to have greater migratory success), wing color (the shade of orange pigmentation in monarchs is a known predictor of migration and flight ability), and the physical density of wings (a measure of wing mass per unit area). We also measured the tear-resistance of wings, using an apparatus that measured the force needed to cause a tear in the wing. Results showed no effect of OE on overall wing size, nor on the shade of orange pigmentation, but a clear effect on measures of physical density and tensile strength. Wings of infected monarchs weighed less per unit area (by 6%), and there was a 20% reduction in tear-resistance of wings. All results were qualitatively similar in a follow-up investigation using freshly-killed specimens. Collectively, this indicates infected monarchs are more prone to wing damage, which would be costly during long-distance migration. As such, this would be one more way in which OE infections reduce migratory success. Given the toll of OE to the monarch population, especially during migration, it would be prudent to focus conservation efforts on mitigating human activities that spread this disease