Inducible defense against pathogens and parasites: optimal choice among multiple options

Defense against pathogen, parasites and herbivores is often enhanced after their invasion into the host's body. Sometimes different options are adopted depending on the identity and the quantity of the pathogen, exemplified by the switch between Th1 and Th2 systems in mammalian immunity. In this paper, we study the optimal defense of the host when two alternative responses are available, which differ in the effectiveness of suppressing the growth of pathogen (parasite, or herbivore), the damage to the host caused by the defense response, and the magnitude of time delay before the defense response becomes fully effective. The optimal defense is the one that minimizes the sum of the damages caused by the pathogen and the cost due to defense activities. The damage by pathogens increases in proportion to the time integral of the pathogen abundance, and the cost is proportional to the defense activity. We can prove that a single globally optimal combination of defense options always exists and there is no other local optimum. Depending on the parameters, the optimal is to adopt only the early response, only the late response, or both responses. The defense response with a shorter time delay is more heavily used when the pathogen grows fast, the initial pathogen abundance is large, and the difference in time delay is long. We also study the host's optimal choice between constitutive and inducible defenses. In the constitutive defense, the response to pathogen attack works without delay, but it causes the cost even when the pathogen attack does not occur. We discuss mammalian immunity and the plant chemical defense from the model's viewpoint.     

Dynamic optimization of host defense, immune memory, and post-infection pathogen levels in mammals

When attacked by pathogens, higher vertebrates produce specific immune cells that fight against them. We here studied the host's optimal schedule of specific immune cell production. The damage caused by the pathogen increases with the pathogen amount in the host integrated over time. On the other hand, there is also a cost incurred by the production of specific immune cells, not only in terms of the energy needed to produce and maintain the cells, but also with respect to damages sustained by the host's body as a result of immune activity. The optimal strategy of the host is the one that minimizes the total cost, defined as a weighted sum of the damage caused by pathogens and the costs caused by the specific immune cells. The problem is solved by using Pontryagin's maximum principle and dynamic programming. The optimal defense schedule is typically as follows: In the initial phase after infection, immune cells are produced at the fastest possible rate. The amount of pathogen increases temporarily but is eventually suppressed. When the pathogen amount is suppressed to a sufficiently low level, the immune cell number decreases and converges to a low steady level, which is maintained by alternately switching between fastest production and no production. We examine the effect of time delay required to have fully active immune cells by comparing cases with different number of rate limiting steps before producing immune cells. We examine the effect of the duration of time (time delay) required before full-scale production of active immune cells by comparing cases with different numbers of rate-limiting steps before immune-cell production. We also discuss the role of immune memory based on the results of the optimal immune reaction.     

Reproductive consequences of transient pathogen exposure across host genotypes and generations

To maximize fitness upon pathogenic infection, host organisms might reallocate energy and resources among life‐history traits, such as reproduction and defense. The fitness costs of infection can result from both immune upregulation and direct pathogen exploitation. The extent to which these costs, separately and together, vary by host genotype and across generations is unknown. We attempted to disentangle these costs by transiently exposing wild isolates and a lab‐domesticated strain of Caenorhabditis elegans nematodes to the pathogen Staphylococcus aureus, using exposure to heat‐killed pathogens to distinguish costs due to immune upregulation and pathogen exploitation. We found that host nematodes exhibit a short‐term delay in offspring production when exposed to live and heat‐killed pathogen, but their lifetime fecundity (total offspring produced) recovered to control levels. We also found genetic variation between host isolates for both cumulative offspring production and magnitude of fitness costs. We further investigated whether there were maternal pathogen exposure costs (or benefits) to offspring and revealed a positive correlation between the magnitude of the pathogen‐induced delay in the parent''s first day of reproduction and the cost to offspring population growth. Our findings highlight the capacity for hosts to recover fecundity after transient exposure to a pathogen.     

Pulmonary eosinophilia and production of MIP-1alpha are prominent responses to infection with pneumonia virus of mice

Human eosinophils secrete two distinct ribonucleases that have antiviral activity against pathogens of the family Paramyxoviridae. To examine the role of eosinophils and their ribonucleases in host defense against paramyxovirus pathogens in vivo, we have developed a mouse model involving a viral pathogen that naturally targets a rodent host. In this work we describe infection of Balb/c mice with pneumonia virus of mice (PVM, strain J3666), a paramyxovirus pathogen found frequently among rodent populations. We show here that pulmonary eosinophilia is an immediate response to infection with PVM, with bronchoalveolar lavage fluid containing 12-14% eosinophils obtained as early as day 3 postinoculation. Infection is accompanied by the production of macrophage inflammatory protein-1-alpha (MIP-1alpha), a chemokine that has been associated with the pulmonary eosinophilia observed in response to respiratory syncytial virus infection in humans and with enhanced clearance of influenza virus in mice. Interestingly, we observed no changes in expression of the chemoattractants eotaxin and RANTES in response to PVM infection, and interleukin-5 remained undetectable throughout. These responses-clinical pathology, viral recovery, pulmonary eosinophilia, and production of MIP-1alpha-will provide a means for exploring the role of eosinophils, eosinophil secretory ribonucleases, and eosinophil chemoattractants in host defense against PVM and related paramyxovirus pathogens in vivo.     

Induction of systemic resistance in plants

When a pathogen is perceived by a host plant, a series of defense responses can be activated. One of these are "local" defenses that occur rapidly at the site of pathogen invasion. Another are "systemic" defenses that are induced in uninoculated parts of the plant. Recently, molecular genetic studies have revealed genes that are signaling components of systemic resistance pathways. Cloning of these genes and characterization of the function of their proteins is now providing insights to processes regulating plant defense against pathogens. Evidence that "systemic" defenses are important for resistance is that when the way is blocked in transgenic plants or in mutants, the plant's defense is compromised. When the pathway is stimulated by exogenous compounds or in mutants, the host resistance is strengthened. A detailed understanding of this pathway is important for both practical and theoretical reasons.     

Costs of resistance and infection by a generalist pathogen

Pathogen infection is typically costly to hosts, resulting in reduced fitness. However, pathogen exposure may also come at a cost even if the host does not become infected. These fitness reductions, referred to as “resistance costs”, are inducible physiological costs expressed as a result of a trade‐off between resistance to a pathogen and aspects of host fitness (e.g., reproduction). Here, we examine resistance and infection costs of a generalist fungal pathogen (Metschnikowia bicuspidata) capable of infecting a number of host species. Costs were quantified as reductions in host lifespan, total reproduction, and mean clutch size as a function of pathogen exposure (resistance cost) or infection (infection cost). We provide empirical support for infection costs and modest support for resistance costs for five Daphnia host species. Specifically, only one host species examined incurred a significant cost of resistance. This species was the least susceptible to infection, suggesting the possibility that host susceptibility to infection is associated with the detectability and size of resistance cost. Host age at the time of pathogen exposure did not influence the magnitude of resistance or infection cost. Lastly, resistant hosts had fitness values intermediate between unexposed control hosts and infected hosts. Although not statistically significant, this could suggest that pathogen exposure does come at some marginal cost. Taken together, our findings suggest that infection is costly, resistance costs may simply be difficult to detect, and the magnitude of resistance cost may vary among host species as a result of host life history or susceptibility.     

The expression of a bean PGIP in transgenic wheat confers increased resistance to the fungal pathogen Bipolaris sorokiniana

A possible strategy to control plant pathogens is the improvement of natural plant defense mechanisms against the tools that pathogens commonly use to penetrate and colonize the host tissue. One of these mechanisms is represented by the host plant's ability to inhibit the pathogen's capacity to degrade plant cell wall polysaccharides. Polygalacturonase-inhibiting proteins (PGIP) are plant defense cell wall glycoproteins that inhibit the activity of fungal endopolygalacturonases (endo-PGs). To assess the effectiveness of these proteins in protecting wheat from fungal pathogens, we produced a number of transgenic wheat lines expressing a bean PGIP (PvPGIP2) having a wide spectrum of specificities against fungal PGs. Three independent transgenic lines were characterized in detail, including determination of the levels of PvPGIP2 accumulation and its subcellular localization and inhibitory activity. Results show that the transgene-encoded protein is correctly secreted into the apoplast, maintains its characteristic recognition specificities, and endows the transgenic wheat with new PG recognition capabilities. As a consequence, transgenic wheat tissue showed increased resistance to digestion by the PG of Fusarium moniliforme. These new properties also were confirmed at the plant level during interactions with the fungal pathogen Bipolaris sorokiniana. All three lines showed significant reductions in symptom progression (46 to 50%) through the leaves following infection with this pathogen. Our results illustrate the feasibility of improving wheat's defenses against pathogens by expression of proteins with new capabilities to counteract those produced by the pathogens.     

GENETIC VARIATION IN RESISTANCE AND FECUNDITY TOLERANCE IN A NATURAL HOST–PATHOGEN INTERACTION

Individuals vary in their ability to defend against pathogens. Determining how natural selection maintains this variation is often difficult, in part because there are multiple ways that organisms defend themselves against pathogens. One important distinction is between mechanisms of resistance that fight off infection, and mechanisms of tolerance that limit the impact of infection on host fitness without influencing pathogen growth. Theory predicts variation among genotypes in resistance, but not necessarily in tolerance. Here, we study variation among pea aphid (Acyrthosiphon pisum) genotypes in defense against the fungal pathogen Pandora neoaphidis. It has been well established that pea aphids can harbor symbiotic bacteria that protect them from fungal pathogens. However, it is unclear whether aphid genotypes vary in defense against Pandora in the absence of protective symbionts. We therefore measured resistance and tolerance to fungal infection in aphid lines collected without symbionts, and found variation among lines in survival and in the percent of individuals that formed a sporulating cadaver. We also found evidence of variation in tolerance to the effects of pathogen infection on host fecundity, but no variation in tolerance of pathogen‐induced mortality. We discuss these findings in light of theoretical predictions about host‐pathogen coevolution.     

How do plants defend themselves against pathogens-Biochemical mechanisms and genetic interventions

In agro-ecosystem, plant pathogens hamper food quality, crop yield, and global food security. Manipulation of naturally occurring defense mechanisms in host plants is an effective and sustainable approach for plant disease management. Various natural compounds, ranging from cell wall components to metabolic enzymes have been reported to protect plants from infection by pathogens and hence provide specific resistance to hosts against pathogens, termed as induced resistance. It involves various biochemical components, that play an important role in molecular and cellular signaling events occurring either before (elicitation) or after pathogen infection. The induction of reactive oxygen species, activation of defensive machinery of plants comprising of enzymatic and non-enzymatic antioxidative components, secondary metabolites, pathogenesis-related protein expression (e.g. chitinases and glucanases), phytoalexin production, modification in cell wall composition, melatonin production, carotenoids accumulation, and altered activity of polyamines are major induced changes in host plants during pathogen infection. Hence, the altered concentration of biochemical components in host plants restricts disease development. Such biochemical or metabolic markers can be harnessed for the development of “pathogen-proof” plants. Effective utilization of the key metabolites-based metabolic markers can pave the path for candidate gene identification. This present review discusses the valuable information for understanding the biochemical response mechanism of plants to cope with pathogens and genomics-metabolomics-based sustainable development of pathogen proof cultivars along with knowledge gaps and future perspectives to enhance sustainable agricultural production.     

A proteomic view of the host-pathogen interaction: The host perspective

The host-pathogen interaction represents a complex and dynamic biological system. The outcome of this interaction is dependent on the microbial pathogen properties to establish infection and the ability of the host to control infection. Although bacterial pathogens have evolved a variety of strategies to subvert host defense functions, several general mechanisms have been shown to be shared among these pathogens. As a result, host effectors that are critical for pathogen entry, survival and replication inside the host cells have become a new paradigm for antimicrobial targeting. This review focuses on the potential utility of a proteomics approach in defining the host-pathogen interaction from the host's perspective.     

Resource limitation has a limited impact on the outcome of virus–fungus co‐infection in an insect host

Infection by pathogens is strongly affected by the diet or condition of the prospective host. Studies that examine the impact of diet have mainly focused on single pathogens; however, co‐infections within a single host are thought to be common. Different pathogen groups might respond differently to resource availability and diverse infections could increase the costs of host defense, meaning the outcome of mixed infections under varying dietary regimes is likely to be hard to predict. We used the generalist cabbage looper, Trichoplusia ni and two of its pathogens, the DNA virus T. ni nucleopolyhedrovirus (TniSNPV) and the entomopathogenic fungus, Beauveria bassiana to examine how nutrient reduction affected the outcome of mixed pathogen infection. We challenged insects with a low or high effective dose of virus, alone or combined with a single dose of fungus. We manipulated food availability after pathogen challenge by diluting artificial diet with cellulose, a non‐nutritious bulking agent, and examined its impact on host and pathogen fitness. Reducing diet quantity did not alter overall or pathogen‐specific mortality. In all cases, TniSNPV‐induced mortality was negatively affected by fungus challenge. Similarly, B. bassiana‐induced mortality was negatively affected by TniSNPV challenge, but only at the higher virus dose. Dietary dilution mainly affected B. bassiana speed of kill when mixed with a high dose of TniSNPV, with an increase in the duration of fungal infection when cellulose was low (high quantity). One pathogen dominated the production of transmission stages in the cadavers and co‐infection did not affect the yield of either pathogen. There was no evidence that co‐infections were more costly to the survivors of pathogen challenge. In conclusion, dietary dilution did not determine the outcome of mixed pathogen infection, but it had more subtle effects, that differed between the two pathogens and could potentially alter pathogen recycling and host–pathogen dynamics.     

细胞核质转运及其受体在植物抗病防御反应中的调控作用

植物病害严重威胁全球粮食生产,研究植物对病原菌防御机制和病原菌对寄主作物的侵染过程和分子机制,有助于改良植物种源使其获得持久抗性。近年来, 日渐增多的研究表明, 一些抗病蛋白需要转移到细胞核内才能启动免疫反应,进而发挥抗病防御作用,而细胞核质转运受体是实现这些抗病蛋白核质转运必不可少的“载体”。因此,细胞核质转运及转运...     

Nucleotide-binding oligomerization domain-like receptors: intracellular pattern recognition molecules for pathogen detection and host defense

The nucleotide binding oligomerization domain-like receptor (NLR) family of pattern recognition molecules is involved in a diverse array of processes required for host immune responses against invading pathogens. Unlike TLRs that mediate extracellular recognition of microbes, several NLRs sense pathogens in the cytosol and upon activation induce host defense signaling pathways. Although TLRs and NLRs differ in their mode of pathogen recognition and function, they share similar domains for microbial sensing and cooperate to elicit immune responses against the pathogen. Genetic variation in several NLR genes is associated with the development of inflammatory disorders or increased susceptibility to microbial infection. Further understanding of NLRs should provide critical insight into the mechanisms of host defense and the pathogenesis of inflammatory diseases.     

Effectors of biotrophic fungi and oomycetes: pathogenicity factors and triggers of host resistance

Many biotrophic fungal and oomycete pathogens share a common infection process involving the formation of haustoria, which penetrate host cell walls and form a close association with plant membranes. Recent studies have identified a class of pathogenicity effector proteins from these pathogens that is transferred into host cells from haustoria during infection. This insight stemmed from the identification of avirulence (Avr) proteins from these pathogens that are recognized by intracellular host resistance (R) proteins. Oomycete effectors contain a conserved translocation motif that directs their uptake into host cells independently of the pathogen, and is shared with the human malaria pathogen. Genome sequence information indicates that oomycetes may express several hundred such host-translocated effectors. Elucidating the transport mechanism of fungal and oomycete effectors and their roles in disease offers new opportunities to understand how these pathogens are able to manipulate host cells to establish a parasitic relationship and to develop new disease-control measures.     

Optimal size of storage for recovery after unpredictable disturbances

Terrestrial plants often live in environments in which above-ground photosynthetic organs (production parts) are suddenly removed by unpredictable disturbances, such as fire, frost, desiccation, pathogen attack, breakage by wind and trampling, or herbivory by insects and mammals. We study the optimal growth schedule for a plant having a below-ground storage organ that is used for recovery (or regrowth) of photosynthetic organs after disturbances. We assume the following: (1) the daily production rate increases with the production part size, but saturates for large size due to shading and local resource depletion, (2) disturbances occur randomly and remove all the aerial parts, (3) plants are finally killed by fatal disturbances that also occur randomly and (4) the plant chooses the pattern of growth, reproduction, storage and recovery after disturbances by reallocation of stored material to maximize the total lifetime reproductive success. The model is analysed by stochastic dynamic programming. The results are as follows: (1) the ratio of storage size to production part size (S/F ratio) is large if the longevity is large and if the disturbance rate is large but a little smaller than the productivity coefficient, (2) the S/F ratio is larger for mature plants than for small immature plants, (3) after disturbances, the above-ground production part recovers relatively quickly, but reproductive activity is depressed until storage size recovers and (4) the variations over time and between habitats differing in disturbance frequency are larger for storage size and for reproductive activity than for production part size. These tendencies are more pronounced for a linear production function (with initial linear increase followed by a sudden stop), but less so for a hyperbolic production function (with a gradually decreasing slope). We also discuss the growth and regrowth behaviour of plants adapted to a disturbance frequency growing under one different disturbance frequency.     

Host-pathogen interactions during apoptosis

Host pathogen interaction results in a variety of responses, which include phagocytosis of the pathogen, release of cytokines, secretion of toxins, as well as production of reactive oxygen species (ROS). Recent studies have shown that many pathogens exert control on the processes that regulate apoptosis in the host. The induction of apoptosis upon infection results from a complex interaction of parasite proteins with cellular host proteins. Abrogation of host cell apoptosis is often beneficial for the pathogen and results in a successful host invasion. However, in some cases, it has been shown that induction of apoptosis in the infected cells significantly imparts protection to the host from the pathogen. There is a strong correlation between apoptosis and the host protein translation machinery: the pathogen makes all possible efforts to modify this process so as to inhibit cell suicide and ensure that it can survive and, in some cases, establish latent infection. This review discusses the significance of various pathways/steps during virus-mediated modulation of host cell apoptosis.     

Characterization of a predominantly pistil-expressed gene encoding a γ-thionin-like protein of Petunia inflata

We isolated a cDNA clone from a pistil cDNA library of Petunia inflata which encodes a protein, PPT, with sequence similarity to -thionins. Characterization of a genomic clone containing a PPT gene revealed the presence of a single intron. Northern analysis revealed that the PPT gene was predominantly expressed in the pistil during all stages of flower development. Since thionins have been implicated in plant defense against pathogens, PPT may play a role similar to that of other defense-related proteins found in the pistil, defending the pistil against pathogen infection.     

Fitness consequences of infection of <Emphasis Type="Italic">Arabidopsis thaliana</Emphasis> with its natural bacterial pathogen <Emphasis Type="Italic">Pseudomonas viridiflava</Emphasis>

Variation in plant resistance to pathogen infection is commonly observed in interactions between wild plants and their foliar pathogens. Models of host–pathogen interactions indicate that a large cost of infection is generally necessary to maintain this variation, yet there is limited evidence that foliar pathogens cause detectable fitness reductions in wild host plants. Most published work has focused on fungal pathogens. Pseudomonas viridiflava, a common bacterial pathogen of the annual weed Arabidopsis thaliana across its range, comprises two distinct genetic clades that cause disease symptoms of different severity. Here we measured the extent of infection of wild A. thaliana populations in the Midwest, USA, and examined the effect on seed production, in field and growth-chamber experiments, of experimental inoculation with isolates from the two clades. We found infection with P. viridiflava varied from 0 to 56% in Midwest A. thaliana populations, with the possibility of several leaves per plant infected later in the growing season. In the growth chambers, experimental inoculation reduced seed set by averages of 15 and 11% for clades A and B, respectively. In the field experiment, only clade A affected plant fitness significantly, reducing seed set by an average of 38%. Underlying these average effects we observed both negative and positive effects of infection, and variation in both fitness among plant genotypes and sensitivity to environmental conditions.     

Sick plants in grassland communities: a growth‐defense trade‐off is the main driver of fungal pathogen abundance

Aboveground fungal pathogens can substantially reduce biomass production in grasslands. However, we lack a mechanistic understanding of the drivers of fungal pathogen infection and impact. Using a grassland global change and biodiversity experiment we show that the trade‐off between plant growth and defense is the main determinant of infection incidence. In contrast, nitrogen addition only indirectly increased incidence via shifting plant communities towards faster growing species. Plant diversity did not decrease incidence, likely because spillover of generalist pathogens or dominance of susceptible plants counteracted negative diversity effects. A fungicide treatment increased plant biomass production and high levels of infection incidence were associated with reduced biomass. However, pathogen impact was context dependent and infection incidence reduced biomass more strongly in diverse communities. Our results show that a growth‐defense trade‐off is the key driver of pathogen incidence, but pathogen impact is determined by several mechanisms and may depend on pathogen community composition.