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1.
Seasonal variation in behavior and physiology, including changes in immune function, are common. This variability is elicited by changes in photoperiod and often covaries with fluctuations in both energy reserves and reproductive state. It is unclear, however, whether changes in either variable alone drive seasonal changes in immunity. We investigated the relative contributions of reproduction and energy balance to changes in immune function. To accomplish this, we uncoupled seasonal changes in reproduction from those related to energy balance via daily injections of N-methyl-d-aspartate (NMDA) in Siberian hamsters (Phodopus sungorus). NMDA is a glutamatergic agonist that blocks short day-induced gonadal regression, while leaving short-day declines in body mass unaffected. In Experiment 1, we examined the effect of differing doses of NMDA on testosterone production as a proxy for NMDA effects on reproduction; a dose-dependent rise in testosterone was observed. In Experiment 2, animals were maintained on long or short days and received daily injections of NMDA. After 8 weeks, all animals underwent a humoral immune challenge. Short-day animals receiving daily injections of NMDA maintained long day-like gonads; however, contrary to our predictions, no trade-off between reproduction or energy balance and immune function was observed. Unexpectedly, NMDA treatment increased immunoglobulin levels in all groups, suggesting that NMDA may provide an immunomodulatory signal, presumably through actions on peripheral glutamate receptors. These results support a previous finding that NMDA blocks reproductive regression. In addition, these findings demonstrate a general immunoenhancing effect of NMDA that appears independent of changes in reproductive or energetic state of the animal.  相似文献   

2.
1.  Organisms must contend with seasonal fluctuations in energy availability. To maintain a positive energy balance year-round, a number of adaptations have evolved including seasonal changes in reproduction, energetics and immunity. Photoperiod is the primary environmental signal most animals use to predict seasonal events. Despite the established link between energetics and immune function, little is known regarding how changes in energy availability affect immunity.
2.  The goal of the present study was to determine the effects of food restriction on photoperiodic changes in reproduction and immune function in the Siberian hamster ( Phodopus sungorus ). Adult hamsters were housed in long or short days and were food restricted or fed ad libitum . Immune responses were quantified by measuring specific antibody production and bacterial killing capacity.
3.  Food restriction decreased body and relative reproductive masses in long-day animals. Antibody responses, but not bacterial killing ability, were enhanced in food restricted short-day animals as compared with ad libitum fed controls. We also found differential effects of body fat on immune responses depending on the immune measure.
4.  The effects of food restriction on immune function appear to vary based on the restriction regimen, the response measured, and the physiological state of the organism including energy balance, metabolic rate and reproductive status.
5.  In conclusion, these results suggest that a wide range of factors can differentially affect immune function. In addition, these effects may vary based on the specific response examined. Future studies should include a variety of measurements to provide a more integrative and accurate picture of reproductive, energetic, and photoperiodic effects on immune function.  相似文献   

3.
Many animals experience marked seasonal fluctuations in environmental conditions. In response, animals display adaptive alterations in physiology and behaviour, including seasonal changes in immune function. During winter, animals must reallocate finite energy stores from relatively costly, less exigent systems (e.g. reproduction and immunity) to systems critical for immediate survival (e.g. thermoregulation). Seasonal changes in immunity are probably mediated by neuroendocrine factors signalling current energetic state. One potential hormonal candidate is insulin, a metabolic hormone released in response to elevated blood glucose levels. The aim of the present study was to explore the potential role of insulin in signalling energy status to the immune system in a seasonally breeding animal, the Siberian hamster (Phodopus sungorus). Specifically, exogenous insulin was administered to male hamsters housed in either long ‘summer-like’ or short ‘winter-like’ days. Animals were then challenged with an innocuous antigen and immune responses were measured. Insulin treatment significantly enhanced humoural immune responses in short, but not long days. In addition, insulin treatment increased food intake and decreased blood glucose levels across photoperiodic treatments. Collectively, these data support the hypothesis that insulin acts as an endocrine signal integrating seasonal energetic changes and immune responses in seasonally breeding rodents.  相似文献   

4.
Among the few existing works on seasonal variation in metabolic rate of polar species, most have been conducted during summer due to logistic constraints and have been focused on species that cease feeding during winter. In this work, we present the first extensive data set on the seasonal variation in metabolic rate of G. antarctica, an abundant amphipod that feeds throughout the year, and its relationship with body size, potential food availability and temperature. We measured the resting metabolic rate (RMR) of groups of individuals during 6 months from late summer through winter at 4 experimental temperatures and for a wide range of body size. RMR had a negative allometric scaling with body size and showed a tendency to increase with temperature as expected. However, temperature and body size effects on RMR showed a significant temporal variation, and an increase in temperature decreased scaling exponents. RMR at the mean seawater temperature throughout the study showed a strong seasonal variation following food availability: RMR decreased from the end of summer through winter, coinciding with a reduction in microphytobenthos stock, but recovered summer values in August, when an epontic algae boom occurred. The seasonal factorial aerobic scope (×2.37) is lower than benthic Antarctic invertebrates that cease feeding during winter, in agreement with what is expected based on theoretical grounds. Results suggest that seasonal variation of RMR would allow G. antarctica to achieve a high efficiency in energy utilization, while maintaining the ability to exploit sudden changes in food supply.  相似文献   

5.
Within individuals, immunity may compete with other life history traits for resources, such as energy and protein, and the damage caused by immunopathology can sometimes outweigh the protective benefits that immune responses confer. However, our understanding of the costs of immunity in the wild and how they relate to the myriad energetic demands on free-ranging organisms is limited. The endangered Galapagos sea lion (Zalophus wollebaeki) is threatened simultaneously by disease from domestic animals and rapid changes in food availability driven by unpredictable environmental variation. We made use of this unique ecology to investigate the relationship between changes in immune activity and changes in body condition. We found that during the first three months of life, changes in antibody concentration were negatively correlated with changes in mass per unit length, skinfold thickness and serum albumin concentration, but only in a sea lion colony exposed to anthropogenic environmental impacts. It has previously been shown that changes in antibody concentration during early Galapagos sea lion development were higher in a colony exposed to anthropogenic environmental impacts than in a control colony. This study allows for the possibility that these relatively large changes in antibody concentration are associated with negative impacts on fitness through an effect on body condition. Our findings suggest that energy availability and the degree of plasticity in immune investment may influence disease risk in natural populations synergistically, through a trade-off between investment in immunity and resistance to starvation. The relative benefits of such investments may change quickly and unpredictably, which allows for the possibility that individuals fine-tune their investment strategies in response to changes in environmental conditions. In addition, our results suggest that anthropogenic environmental impacts may impose subtle energetic costs on individuals, which could contribute to population declines, especially in times of energy shortage.  相似文献   

6.
In temperate regions, an organism's ability to rapidly adapt to seasonally varying environments is essential for its survival. In response to seasonal changes in selection pressure caused by variation in temperature, humidity, and food availability, some organisms exhibit plastic changes in phenotype. In other cases, seasonal variation in selection pressure can rapidly increase the frequency of genotypes that offer survival or reproductive advantages under the current conditions. Little is known about the relative influences of plastic and genetic changes in short‐lived organisms experiencing seasonal environmental fluctuations. Cold hardening is a seasonally relevant plastic response in which exposure to cool, but nonlethal, temperatures significantly increases the organism's ability to later survive at freezing temperatures. In the present study, we demonstrate seasonal variation in cold hardening in Drosophila melanogaster and test the extent to which plasticity and adaptive tracking underlie that seasonal variation. We measured the post‐cold hardening freeze tolerance of flies from outdoor mesocosms over the summer, fall, and winter. We bred outdoor mesocosm‐caught flies for two generations in the laboratory and matched each outdoor cohort to an indoor control cohort of similar genetic background. We cold hardened all flies under controlled laboratory conditions and then measured their post‐cold hardening freeze tolerance. Comparing indoor and field‐caught flies and their laboratory‐reared G1 and G2 progeny allowed us to determine the roles of seasonal environmental plasticity, parental effects, and genetic changes on cold hardening. We also tested the relationship between cold hardening and other factors, including age, developmental density, food substrate, presence of antimicrobials, and supplementation with live yeast. We found strong plastic responses to a variety of field‐ and laboratory‐based environmental effects, but no evidence of seasonally varying parental or genetic effects on cold hardening. We therefore conclude that seasonal variation in post‐cold hardening freeze tolerance results from environmental influences and not genetic changes.  相似文献   

7.
The arctic fox (Alopex lagopus) is a medium-sized predator of the high Arctic experiencing extreme seasonal fluctuations in food availability, photoperiod and temperature. In this study, the plasma leptin, ghrelin and growth hormone (GH) concentrations of male arctic foxes were determined during a food deprivation period of 13 days and the subsequent recovery in November and May. Leptin, ghrelin and GH were present in arctic fox plasma in amounts comparable to other carnivores. The plasma leptin concentrations did not react to food deprivation unlike in humans and rodents. However, the leptin levels increased during re-feeding as an indicator of increasing energy reserves. The relatively high ghrelin–leptin ratio, decrease in the plasma ghrelin concentration, an increase in the circulating GH concentrations and the observed negative correlation between plasma ghrelin and free fatty acid levels during fasting suggest that these hormones take part in the weight-regulation and energy metabolism of this species by increasing fat utilisation during food deprivation. The results strengthen the hypothesis that the actions of these weight-regulatory hormones are species–specific and depend on seasonality and the life history of the animals.Abbreviations FFA free fatty acid - GH growth hormone - RMR resting metabolic rate Communicated by G. Heldmaier  相似文献   

8.
Quantifying diet is essential for understanding the functional role of species with regard to energy processing, transfer, and storage within ecosystems. Recently, variance structure in the stable isotope composition of consumer tissues has been touted as a robust tool for quantifying trophic niche width, a task that has previously proven difficult due to bias in direct dietary analyses and difficulties in integrating diet composition over time. We used carbon and nitrogen stable isotope analyses to examine trophic niche width of two sympatric aquatic snakes, banded watersnakes Nerodia fasciata and black swamp snakes Seminatrix pygaea inhabiting an isolated wetland where seasonal migrations of amphibian prey cause dramatic shifts in resource availability. Specifically, we characterized snake and prey isotope compositions through time, space, and ontogeny and examined isotope values in relation to prey availability and snake diets assessed by gut content analysis. We determined that prey cluster into functional groups based on similarity of isotopic composition and seasonal availability. Isotope variance structure indicated that the trophic niche width of the banded watersnake was broader (more generalist) than that of the black swamp snake. Banded watersnakes also exhibited seasonal variation in isotope composition, suggesting seasonal diet shifts that track amphibian prey availability. Conversely, black swamp snakes exhibited little seasonal variation but displayed strong ontogenetic shifts in carbon and nitrogen isotope composition that closely paralleled ontogenetic shifts in their primary prey, paedomorphic mole salamanders Ambystoma talpoideum. Although niche dimensions are often treated as static, our results demonstrate that seasonal shifts in niche dimensions can lead to changes in niche overlap between sympatric species. Such short‐term fluctuations in niche overlap can influence competitive interactions and consequently the composition and dynamics of communities and ecosystems.  相似文献   

9.
Studies demonstrate the importance of metabolic resources in the regulation of reproduction and immune functions in seasonal breeders. In this regard, the restricted energy availability can be considered as an environmental variable that may act as a seasonal stressor and can lead to compromised immune functions. The present study explored the effect of photoperiodic variation in the regulation of immune function under metabolic stress condition. The T-cell-dependent immune response in a tropical seasonal breeder Funambulus pennanti was studied following the inhibition of cellular glucose utilization with 2-deoxy-d-glucose (2-DG). 2-DG treatment resulted in the suppression of general (e.g., proliferative response of lymphocytes) and antigen-specific [anti-keyhole limpet hemocyanin IgG titer and delayed-type hypersensitivity response] T-cell responses with an activation of the hypothalamic–pituitary–adrenal axis, which was evident from the increased levels of plasma corticosterone. 2-DG administration increased the production of inflammatory cytokines [interleukin (IL)-1β and tumor necrosis factor (TNF)-α] and decreased the autocrine T-cell growth factor IL-2. The immunocompromising effect of 2-DG administration was retarded in animals exposed to short photoperiods compared with the control and long photoperiod-exposed groups. This finding suggested that short photoperiodic conditions enhanced the resilience of the immune system, possibly by diverting metabolic resources from the reproductive organs toward the immune system. In addition, melatonin may have facilitated the energy “trade-off” between reproductive and immune mechanisms, thereby providing an advantage to the seasonal breeders for their survival during stressful environmental conditions.  相似文献   

10.
Seasonal adjustments in body mass and thermogenesis are important for the survival of small mammals during acclimatization in the temperate zone. To determine the contributions of short photoperiod and cold temperatures to seasonal changes in thermogenesis and body mass in Mongolian gerbils (Meriones unguiculatus), body mass, basal metabolic rate (BMR), nonshivering thermogenesis (NST), energy intake and energy digestibility were determined in seasonally acclimatized and laboratory acclimated animals. Body mass showed significant seasonal changes and decreased to a minimum in winter. Both BMR and NST increased in winter, and these changes were mimicked by exposing animals to short photoperiod or cold temperatures in the animal house. Digestible energy intake also increased significantly in winter, and also during exposure of housed animals to both short photoperiod and cold. These results suggest that Mongolian gerbils overcome winter thermoregulatory challenges by increasing energy intake and thermogenesis, and decreasing body mass to reduce total energy requirements. Short photoperiod and cold can serve as effective environmental cues during seasonal acclimatization.  相似文献   

11.
In birds, the period spent brooding or guarding young chicks is highly variable, but such variation has seldom been studied. Previous single‐year studies of Antarctic petrels Thalassoica antarctica and grey‐headed albatrosses Thalassarche chrysostoma revealed a pronounced seasonal decline in brood‐guarding duration and gave rise to the ‘synchronisation hypothesis’, which suggests that some of the variation in the length of the brood‐guarding stage is related to predictable seasonal changes in the risk of chick predation. We tested the predictions of this and three other hypotheses in a two‐site, four‐year study of the black‐browed albatross T. melanophris. The existence of a pronounced seasonal decline in brood‐guarding duration was apparent at both sites, and in years of contrasting food availability, providing further support for the ‘synchronisation hypothesis’. Alternative explanations for this pattern are that short brood‐guarding periods for late‐hatched chicks result from a seasonal decline in food availability or from the fact that early nesting birds are of higher individual quality. However, these explanations are at odds with the absence of a seasonal decline in early chick growth or in probability of chick survival. Furthermore, adult quality (measured as past reproductive performance) had a weak and inconsistent effect on the duration of brood‐guarding. Weather changes explained some of the variation in brood‐guarding, but there were no differences between regions of contrasting climates. Individual pairs displayed a degree of inter‐annual consistency in brood‐guarding duration and, at least in some years, longer brood‐guarding resulted in higher fledging probability. We speculate that a higher investment in brood‐guarding increases the cost of reproduction, which counteracts other selective pressures that would otherwise lead to longer brood‐guarding durations.  相似文献   

12.
To maximize the effectiveness of conservation interventions, it is crucial to have an understanding of how intraspecific variation determines the relative importance of potential limiting factors. For bird populations, limiting factors include nest‐site availability and foraging resources, with the former often addressed through the provision of artificial nestboxes. However, the effectiveness of artificial nestboxes depends on the relative importance of nest‐site vs. foraging resource limitations. Here, we investigate factors driving variation in breeding density, nestbox occupation and productivity in two contrasting study populations of the European Roller Coracias garrulus, an obligate cavity‐nesting insectivorous bird. Breeding density was more than four times higher at the French study site than at the Latvian site, and there was a positive correlation between breeding density (at the 1‐km2 scale) and nest‐site availability in France, whereas there was a positive correlation between breeding density and foraging resource availability in Latvia. Similarly, the probability of a nestbox being occupied increased with predicted foraging resource availability in Latvia but not in France. We detected no positive effect of foraging resource availability on productivity at either site, with most variation in breeding success driven by temporal effects: a seasonal decline in France and strong interannual fluctuations in Latvia. Our results indicate that the factors limiting local breeding density can vary across a species' range, resulting in different conservation priorities. Nestbox provisioning is a sufficient short‐term conservation solution at our French study site, where foraging resources are typically abundant, but in Latvia the restoration of foraging habitat may be more important.  相似文献   

13.
The metabolic and water evaporation strategies in spiders may be part of a set of physiological adaptations to tolerate low or unpredictable food availability, buffering spiders against environmental fluctuations such as those of the high mountains of the central Andes.The aim of this study is to analyze experimentally the variations in metabolic rate and the rate of evaporative water with food and/or water restriction in a high mountain mygalomorph spider population (Paraphysa sp.).We found that the low metabolism of this spider was not affected by water restriction, but its metabolism was depressed after 3 weeks of food deprivation. The spider did not show seasonal metabolic changes but it presented seasonal changes in the rate of evaporative water loss at high temperatures.Females with egg sacs reduced their metabolic rate and evaporative water at high temperatures.These findings constitute a set of possible adaptations to a highly fluctuating Mediterranean environment, which is completely covered with snow for many months and then progresses rapidly to a very dry climate with high temperatures.  相似文献   

14.
Many animals rely on stored energy through periods of high energy demand or low energy availability or both. A variety of mechanisms may be employed to attain and conserve energy for such periods. Wild grey seals demonstrate seasonal patterns of energy storage and foraging behaviour that appear to maximize the allocation of energy to reproduction—a period characterized by both high energy demand and low food availability. We examined seasonal patterns in resting rates of oxygen consumption as a proxy for metabolic rate (RMR) and body composition in female grey seals (four adults and six juveniles), testing the hypothesis that adults would show seasonal changes in RMR related to the reproductive cycle but that juveniles would not. There was significant seasonal variation in rates of resting oxygen consumption of adult females, with rates being highest in the spring and declining through the summer months into autumn. This variation was not related to changes in water temperature. Adults increased in total body mass and in fat content during the same spring to autumn period that RMR declined. RMR of juveniles showed no clear seasonal patterns, but did increase with increasing mass. These data support the hypothesis that seasonal variation in RMR in female grey seals is related to the high costs of breeding.  相似文献   

15.
Non-tropical rodents undergo seasonal changes in immune function and disease. It has been hypothesized that seasonal fluctuations in immunity of non-tropical rodents are due to suppressed immune function during harsh winter conditions. A logical extension of this hypothesis is that seasonal changes in immunity should be reduced or absent in tropical rodents that do not experience marked seasonal fluctuations in environmental conditions; however this hypothesis remains to be tested. The present study tested the effects of photoperiod on humoral and cell-mediated immune function of male Aztec mice ( Peromyscus aztecus hylocetes). P. a. hylocetes were housed in long (L:D 16:8) or short days (L:D 8:16) for 10 weeks. Animals were then immunized with the antigen keyhole limpet hemocyanin (KLH). Serum anti-KLH immunoglobulin G (IgG) concentrations and splenocyte proliferation in response to the T-cell mitogen Concanavalin A were assessed. Short-day P. a. hylocetes did not display differences in reproductive or immune measures compared with long-day mice. Collectively, these results suggest that P. a. hylocetes are reproductively and immunologically non-responsive to photoperiod. This lack of immunological responsiveness is likely due to the relative seasonal stability of their environment compared with temperate zone species.  相似文献   

16.
Many birds exhibit considerable phenotypic flexibility in metabolism to maintain thermoregulation or to conserve energy. This flexibility usually includes seasonal variation in metabolic rate. Seasonal changes in physiology and behavior of birds are considered to be a part of their adaptive strategy for survival and reproductive success. House Sparrows (Passer domesticus) are small passerines from Europe that have been successfully introduced to many parts of the world, and thus may be expected to exhibit high phenotypic flexibility in metabolic rate. Mass specific Resting Metabolic Rate (RMR) and Basal Metabolic Rate (BMR) were significantly higher in winter compared with summer, although there was no significant difference between body mass in summer and winter. A similar, narrow thermal neutral zone (25–28 °C) was observed in both seasons. Winter elevation of metabolic rate in House Sparrows was presumably related to metabolic or morphological adjustments to meet the extra energy demands of cold winters. Overall, House Sparrows showed seasonal metabolic acclimatization similar to other temperate wintering passerines. The improved cold tolerance was associated with a significant increase in VO2 in winter relative to summer. In addition, some summer birds died at 5 °C, whereas winter birds did not, further showing seasonal variation in cold tolerance. The increase in BMR of 120% in winter, compared to summer, is by far the highest recorded seasonal change so far in birds.  相似文献   

17.
Seasonal dormancy is a widespread mechanism for reducing energy expenditure during periods of low energy availability. Seasonal variation in activity and the cost of pumping water through the siphons were investigated to estimate the importance of activity regulation to the seasonal energy budget of the Antarctic clam, Laternula elliptica. In the laboratory, a metabolic rate of 26.35 μmol O2 h−1 was estimated for a 50-mm shell length L. elliptica pumping water at −0.4 °C. In the field, the proportion of time siphons were visible at the sediment surface varied seasonally (32% visible in June/July compared to 86% in December/January). L. elliptica were actively pumping for a minimum of 19% of each 24-h period during winter (August) compared to a summer maximum when animals were actively pumping for 73% of the time (February). This resulted in a 3.7-fold seasonal difference in the calculated energy consumption of a 50-mm L. elliptica (19.2 μmol O2 h−1 in February versus 5.0 μmol O2 h−1 in August), which closely matches the 3.0-fold seasonal variation in metabolic rate found previously. Seasonal variation in activity could therefore be responsible for much of the seasonal difference in energy consumption of L. elliptica. Inter-annual variation in timing of the seasonal activity maxima (January 2004 and March 1999) was correlated with variation in the timing of the summer plankton bloom in Ryder Bay. In the laboratory, periods of extended siphon closure (133 ± 114 min, mean ± SD) were accompanied by long periods of heart arrhythmia (167 ± 135 min), during which time blood oxygen levels dropped to values close to zero. Heart arrhythmia is most likely part of a hypo-metabolic adaptation to reduce energy costs during extended periods of siphon closure. Physiological and behavioural dormancy, with associated hypoxia tolerance, appear to be key mechanisms controlling the seasonal energy budget of L. elliptica.  相似文献   

18.
Munessa Forest is a mountain forest in south-eastern Ethiopia experiencing seasonal rainfall variation. We investigated seasonal cambial activity and dormancy from increment rates of four different tree species belonging to varying life forms, namely, evergreen native conifer (Podocarpus falcatus), evergreen introduced conifer (Pinus patula), evergreen broadleaved tree (Prunus africana) and deciduous broadleaved tree (Celtis africana). Measurements of stem radius fluctuations were registered with the help of high-resolution electronic dendrometers. Daily amplitudes of stem diameter variations and daily and monthly net growth rates were determined and related to climatic variables measured at local climate stations. Thin sections of wood collected with a microcorer every 3–6 weeks allowed a visual control of newly formed wood cells during consecutive time intervals. Lack of water availability during the long dry season induced cambial dormancy of 5–7 months depending on life forms. After the onset of the short rainy season, stem swelling started quite synchronously with a variation of only single days in all studied species. Evergreen tree species were able to initiate wood formation during the short rainy season, whereas growth in the deciduous broadleaved species started in the long rainy season. The acquired data provide a basis for delineating the species-specific growth boundaries and the duration of the cambial growing season.  相似文献   

19.
The seasonal availability of food resources is an important factor shaping the life‐history strategies of organisms. During times of nutritional restriction, physiological trade‐offs can induce periods of immune suppression, thereby increasing susceptibility to infectious disease. Our goal was to provide a conceptual framework describing how the endemic level bovine brucellosis (Brucella abortus) may be maintained in Yellowstone bison based on the seasonality of food resources and the life‐history strategies of the host and pathogen. Our analysis was based on active B. abortus infection (measured via bacterial culture), nutritional indicators (measured as metabolites and hormones in plasma), and carcass measurements of 402 slaughtered bison. Data from Yellowstone bison were used to investigate (1) whether seasonal changes in diet quality affect nutritional condition and coincide with the reproductive needs of female bison; (2) whether active B. abortus infection and infection intensities vary with host nutrition and nutritional condition; and (3) the evidence for seasonal changes in immune responses, which may offer protection against B. abortus, in relation to nutritional condition. Female bison experienced a decline in nutritional condition during winter as reproductive demands of late gestation increased while forage quality and availability declined. Active B. abortus infection was negatively associated with bison age and nutritional condition, with the intensity of infection negatively associated with indicators of nutrition (e.g., dietary protein and energy) and body weight. Data suggest that protective cell‐mediated immune responses may be reduced during the B. abortus transmission period, which coincides with nutritional insufficiencies and elevated reproductive demands during spring. Our results illustrate how seasonal food restriction can drive physiological trade‐offs that suppress immune function and create infection and transmission opportunities for pathogens.  相似文献   

20.
In an effort to suppress microbial outgrowth, the host sequesters essential nutrients in a process termed nutritional immunity. However, inflammatory responses to bacterial insult can restore nutritional resources. Given that nutrient availability modulates virulence factor production and biofilm formation by other bacterial species, we hypothesized that fluctuations in heme-iron availability, particularly at privileged sites, would similarly influence Haemophilus biofilm formation and pathogenesis. Thus, we cultured Haemophilus through sequential heme-iron deplete and heme-iron replete media to determine the effect of transient depletion of internal stores of heme-iron on multiple pathogenic phenotypes. We observed that prior heme-iron restriction potentiates biofilm changes for at least 72 hours that include increased peak height and architectural complexity as compared to biofilms initiated from heme-iron replete bacteria, suggesting a mechanism for epigenetic responses that participate in the changes observed. Additionally, in a co-infection model for human otitis media, heme-iron restricted Haemophilus, although accounting for only 10% of the inoculum (90% heme-iron replete), represented up to 99% of the organisms recovered at 4 days. These data indicate that fluctuations in heme-iron availability promote a survival advantage during disease. Filamentation mediated by a SulA-related ortholog was required for optimal biofilm peak height and persistence during experimental otitis media. Moreover, severity of disease in response to heme-iron restricted Haemophilus was reduced as evidenced by lack of mucosal destruction, decreased erythema, hemorrhagic foci and vasodilatation. Transient restriction of heme-iron also promoted productive invasion events leading to the development of intracellular bacterial communities. Taken together, these data suggest that nutritional immunity, may, in fact, foster long-term phenotypic changes that better equip bacteria for survival at infectious sites.  相似文献   

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