Immune gene expression and epigenetic potential affect the consumption of risky food by female house sparrows.

When organisms move into new areas, they are likely to encounter novel food resources. Even if they are nutritious, these foods can also be risky, as they might be contaminated by parasites. The behavioural immune system of animals could help them avoid the negative effects of contaminated resources, but our understanding of behavioural immunity is limited, particularly whether and how behavioural immunity interacts with physiological immunity. Here, we asked about the potential for interplay between these two traits, specifically how the propensity of an individual house sparrow (Passer domesticus) to take foraging risks was related to its ability to regulate a key facet of its immune response to bacterial pathogens. Previously, we found that sparrows at expanding geographic range edges were more exploratory and less risk-averse to novel foods; in those same populations, birds tended to over-express Toll-like receptor 4 (TLR4), a pattern-recognition receptor that distinguishes cell-wall components of Gram-negative bacteria, making it the major sensor of potentially lethal gut microbial infections including salmonellosis. When we investigated how birds would respond to a typical diet (i.e., mixed seeds) spiked with domesticated chicken faeces, birds that expressed more TLR4 or had higher epigenetic potential for TLR4 (more CpG dinucleotides in the putative gene promoter) ate more food, spiked or not. Females expressing abundant TLR4 were also willing to take more foraging risks and ate more spiked food. In males, TLR4 expression was not associated with risk-taking. Altogether, our results indicate that behaviour and immunity covary among individual house sparrows, particularly in females where those birds that maintain more immune surveillance also are more disposed to take foraging risks.

"Submergence" of Western equine encephalitis virus: Evidence of positive selection argues against genetic drift and fitness reductions.

Understanding the circumstances under which arboviruses emerge is critical for the development of targeted control and prevention strategies. This is highlighted by the emergence of chikungunya and Zika viruses in the New World. However, to comprehensively understand the ways in which viruses emerge and persist, factors influencing reductions in virus activity must also be understood. Western equine encephalitis virus (WEEV), which declined during the late 20th century in apparent enzootic circulation as well as equine and human disease incidence, provides a unique case study on how reductions in virus activity can be understood by studying evolutionary trends and mechanisms. Previously, we showed using phylogenetics that during this period of decline, six amino acid residues appeared to be positively selected. To assess more directly the effect of these mutations, we utilized reverse genetics and competition fitness assays in the enzootic host and vector (house sparrows and Culex tarsalis mosquitoes). We observed that the mutations contemporary with reductions in WEEV circulation and disease that were non-conserved with respect to amino acid properties had a positive effect on enzootic fitness. We also assessed the effects of these mutations on virulence in the Syrian-Golden hamster model in relation to a general trend of increased virulence in older isolates. However, no change effect on virulence was observed based on these mutations. Thus, while WEEV apparently underwent positive selection for infection of enzootic hosts, residues associated with mammalian virulence were likely eliminated from the population by genetic drift or negative selection. These findings suggest that ecologic factors rather than fitness for natural transmission likely caused decreased levels of enzootic WEEV circulation during the late 20th century.

The causative effects of corticosterone on innate immunity during the stress response in the House Sparrow, Passer domesticus.

Stress-induced inhibition of innate immune activity has been observed in a variety of wild birds and may increase chances of infection because this activity constitutes the first line of defense against pathogens. We previously reported that the transient elevation of plasma corticosterone (CORT; the primary avian glucocorticoid) that occurs during stress is necessary for stress-induced suppression of natural antibody-mediated, complement-mediated, and bactericidal activity. Here, we further investigated the regulatory role of CORT during this suppression. To this end, we treated House Sparrows (Passer domesticus) with mitotane to block endogenous CORT production, administered CORT at one of three doses (HI: 1.34 mg/kg; LO: 1.00 mg/kg; CON: vehicle), and assessed natural antibody-mediated, complement-mediated, and bactericidal activity during acute stress induced by handling and restraint. Mitotane administration eliminated the endogenous plasma CORT increase that normally takes place during stress, and corticosterone treatment increased plasma CORT to levels similar to those measured in intact birds during acute stress. As predicted, mitotane-treated birds receiving CON injections did not exhibit stress-induced suppression of complement-mediated and bactericidal activity, and CORT administration at both LO and HI doses restored this suppression. Contrary to expectations, mitotane-treated birds receiving CON injections demonstrated stress-induced suppression of natural antibody-mediated activity. Furthermore, CORT administration did not influence this parameter. These results suggest that stress inhibits innate immune activity through both CORT-dependent and CORT-independent mechanisms, but the contribution of these mechanisms can vary. This variation may result from effects of environmental factors, the identity and role of which warrant further research.

Alternative reproductive strategies in white-throated sparrows are associated with differences in parasite load following experimental infection.

Immune defences often trade off with other life-history components. Within species, optimal allocation to immunity may differ between the sexes or between alternative life-history strategies. White-throated sparrows (Zonotrichia albicollis) are unusual in having two discrete plumage morphs, white-striped and tan-striped. Within each sex, white-striped individuals are more aggressive and provide less parental care than tan-striped individuals. We extended immunocompetence handicap models, which predict sex differences in immunity and parasitism, to hypothesize that infection susceptibility should be greater in white-striped than tan-striped birds. We inoculated birds of both morphs with malarial parasites. Contrary to our prediction, among birds that became infected, parasite loads were higher in tan-striped than white-striped individuals and did not differ between the sexes. Circulating androgen levels did not differ between morphs but were higher in males than females. Our findings are not consistent with androgen-mediated immunosuppression. Instead, morph differences in immunity could reflect social interactions or life-history-related differences in risk of injury, and/or genetic factors. Although plumage and behavioural morphs of white-throated sparrow may differ in disease resistance, these differences do not parallel sex differences that have been reported in animals, and do not appear to be mediated by differences in androgen levels.

Corticosterone rapidly suppresses innate immune activity in the house sparrow (Passer domesticus).

Stress-induced effects on innate immune activity in wild birds have been difficult to predict. These difficulties may arise from the frequent assumptions that (1) the stress response influences different components of the immune response similarly, (2) stress-induced effects do not change over the course of the stress response and (3) glucocorticoids are the primary regulators of stress-induced changes of immune activity. We tested the first two assumptions by measuring three components of innate immunity at two times during the stress response in captive adult male house sparrows, Passer domesticus Acute stress resulting from handling and restraint suppressed plasma lytic and microbicidal activity within 10 min and reduced plasma agglutination ability within 120 min. We tested the third assumption by measuring stress-induced effects in sparrows that were pharmacologically adrenalectomized by mitotane administration. Confirming the effectiveness of this treatment, mitotane-treated birds had lower pre-stress plasma CORT than control birds and showed no increase in plasma CORT during acute stress. The innate immune activity of mitotane-treated birds did not decrease during the stress response, but the pre-stress immune activity of these birds did not differ from that of vehicle-treated birds. These results suggest that elevated plasma CORT during stress is primarily responsible for mediating stress-induced suppression of innate immune activity.

Costs of immunity and their role in the range expansion of the house sparrow in Kenya.

There are at least two reasons to study traits that mediate successful range expansions. First, dispersers will found new populations and thus impact the distribution and evolution of species. Second, organisms moving into new areas will influence the fate of resident communities, directly competing with or indirectly affecting residents by spreading non-native or spilling-back native parasites. The success of invaders in new areas is likely mediated by a counterbalancing of costly traits. In new areas where threats are comparatively rare, individuals that grow rapidly and breed prolifically should be at an advantage. High investment in defenses should thus be disfavored. In the present study, we compared the energetic, nutritional and collateral damage costs of an inflammatory response among Kenyan house sparrow (Passer domesticus) populations of different ages, asking whether costs were related to traits of individuals from three different capture sites. Kenya is among the world's most recent range expansions for this species, and we recently found that the expression of Toll-like receptors (TLRs), leukocyte receptors that instigate inflammatory responses when bound to microbial elements, was related to the range expansion across the country. Here, we found (contrary to our expectations) that energetic and nutritional costs of inflammation were higher, but damage costs were lower, in range-edge compared with core birds. Moreover, at the individual level, TLR-4 expression was negatively related to commodity costs (energy and a critical amino acid) of inflammation. Our data thus suggest that costs of inflammation, perhaps mediated by TLR expression, might mitigate successful range expansions.

Population Differences at MHC Do Not Explain Enhanced Resistance of Song Sparrows to Local Parasites.

Infectious disease represents an emerging threat to natural populations, particularly when hosts are more susceptible to novel parasites (allopatric) than to parasites from the local area (sympatric). This pattern could arise through evolutionary processes (host populations become adapted to their local parasites and genetically differentiated from other populations at immune-related loci) and/or through ecological interactions (host individuals develop resistance to local parasites through previous exposure). The relative importance of these candidate mechanisms remains unclear. In jawed vertebrates, genes of the major histocompatibility complex (MHC) play a fundamental role in immunity and are compelling candidates for spatially varying selection. We recently showed that song sparrows (Melospiza melodia) are more susceptible to allopatric than to sympatric strains of malaria (Plasmodium). In the current study, to determine whether population differences at MHC explain this pattern, we characterized the peptide-binding regions of MHC (classes I and II) of birds that did or did not become infected in the previous experiment. We recovered up to 4 alleles per individual at class I, implying at least 2 loci, and up to 26 alleles per individual at class II, implying at least 13 loci. Individuals with more class I alleles were less likely to become infected by Plasmodium, consistent with parasite-mediated balancing selection. However, we found no evidence for population genetic differentiation at either class of MHC, based on 36 individuals sequenced. Resistance to sympatric parasites previously described for this system likely stems from individuals' prior immune experience, not from population differentiation and locally protective alleles at MHC.

Captivity influences immune responses, stress endocrinology, and organ size in house sparrows (Passer domesticus).

Studies using wild animals in laboratory-based research require bringing wild-captured organisms into a novel setting, which can have long-lasting impacts on physiology and behavior. In several species, captivity stimulates stress hormone production and can alter immune function. Despite this, there is little consensus on how captivity influences stress hormone regulation, or if captivity-induced changes in stress hormone production and regulation mediate changes in immune function. In this study, we investigate the influence of captivity on the physiology of a wild bird commonly-used in laboratory-based research, the house sparrow (Passer domesticus). We tested how captivity influences stress endocrinology, immune responses, and organ mass, and also investigated if the production or regulation of corticosterone, the main stress hormone in birds, correlated with changes in immunity. We found that baseline corticosterone concentrations and maximum capacity of the adrenals to secrete corticosterone increase following captivity and remain elevated after 9weeks of captivity. A measure of innate immune function, the bactericidal ability of plasma, also increased with time spent in captivity. Wound healing was also influenced by time spent in captivity, with birds taking almost 2days longer to heal if they were wounded after 3weeks in captivity when compared with birds that were wounded immediately upon capture. Additionally, captivity caused notable reductions in spleen and liver mass. Together, these results imply that captivity can have long-lasting effects on house sparrow corticosterone release and immune function, and suggest that even after 9weeks house sparrows do not acclimate physiologically to life in captivity.

Life-history dependent relationships between body condition and immunity, between immunity indices in male Eurasian tree sparrows.

In free-living animals, recent evidence indicates that innate, and acquired, immunity varies with annual variation in the demand for, and availability of, food resources. However, little is known about how animals adjust the relationships between immunity and body condition, and between innate and acquired immunity to optimize survival over winter and reproductive success during the breeding stage. Here, we measured indices of body condition (size-corrected mass [SCM], and hematocrit [Hct]), constitutive innate immunity (plasma total complement hemolysis activity [CH50]) and acquired immunity (plasma immunoglobulin A [IgA]), plus heterophil/lymphocyte (H/L) ratios, in male Eurasian tree sparrows (Passer montanus) during the wintering and the breeding stages. We found that birds during the wintering stage had higher IgA levels than those from the breeding stage. Two indices of body condition were both negatively correlated with plasma CH50 activities, and positively with IgA levels in wintering birds, but this was not the case in the breeding birds. However, there was no correlation between CH50 activities and IgA levels in both stages. These results suggest that the relationships between body condition and immunity can vary across life-history stage, and there are no correlations between innate and acquired immunity independent of life-history stage, in male Eurasian tree sparrows. Therefore, body condition indices predict immunological state, especially during the non-breeding stage, which can be useful indicators of individual immunocompetences for understanding the variations in innate and acquired immunity in free-living animals.

Covariation in stress and immune gene expression in a range expanding bird.

The enemy release hypothesis (ERH) posits that hosts encounter fewer infectious parasites when they arrive in new areas, so individuals that adjust their immune defenses most effectively should thrive and even expand the range of that species. An important aspect of vertebrate immune defense is inflammation, as it provides rapid defense against diverse parasites. Glucocorticoids (GCs) are integral to the regulation of inflammation, so here we investigated whether and how covariation in the expression of genes affecting the regulation of inflammation and GCs might have impacted the house sparrow (Passer domesticus) invasion of Kenya. Toll-like receptors 2 and 4 (TLRs) detect microbial threats and instigate inflammatory responses, whereas the glucocorticoid receptor (GR) is integral to resolving inflammation via both local and systemic pathways. As with a previous study on circulating leukocytes, we found that splenic TLR-4 and TLR-2 (the latter marginally non-significant) expression was higher in younger than older populations but only when differences in spleen size were considered; birds at the range edge had larger spleens. In regards to covariation, we found that TLR-2, TLR-4 and GR expression were closely inter-related within individuals, but covariation did not differ among populations. Subsequently, our data suggest that house sparrows are using variants of a common stress-immune regulatory mechanism to expand their Kenyan range.

A blurring of life-history lines: Immune function, molt and reproduction in a highly stable environment.

Rufous-collared sparrows (Zonotrichia capensis peruviensis) from valleys in the Atacama Desert of Chile, live in an extremely stable environment, and exhibit overlap in molt and reproduction, with valley-specific differences in the proportion of birds engaged in both. To better understand the mechanistic pathways underlying the timing of life-history transitions, we examined the relationships among baseline and stress-induced levels of corticosterone (CORT), testosterone, and bacteria-killing ability of the blood plasma (BKA), as well as haemosporidian parasite infections and the genetic structure of two groups of sparrows from separate valleys over the course of a year. Birds neither molting nor breeding had the lowest BKA, but there were no differences among the other three categories of molt-reproductive stage. BKA varied over the year, with birds in May/June exhibiting significantly lower levels of BKA than the rest of the year. We also documented differences in the direction of the relationship between CORT and BKA at different times during the year. The direction of these relationships coincides with some trends in molt and reproductive stage, but differs enough to indicate that these birds exhibit individual-level plasticity, or population-level variability, in coordinating hypothalamo-pituitary-adrenal axis activity with life-history stage. We found weak preliminary evidence for genetic differentiation between the two populations, but not enough to indicate genetic isolation. No birds were infected with haemosporidia, which may be indicative of reduced parasite pressure in deserts. The data suggest that these birds may not trade off among different life-history components, but rather are able to invest in multiple life-history components based on their condition.

Among- and within-individual correlations between basal and maximal metabolic rates in birds.

The aerobic capacity model proposes that endothermy is a by-product of selection favouring high maximal metabolic rates (MMR) and its mechanistic coupling with basal metabolic rate (BMR). Attempts to validate this model in birds are equivocal and restricted to phenotypic correlations (rP), thus failing to distinguish among- and within-individual correlations (rind and re). We examined 300 paired measurements of BMR and MMR from 60 house sparrows before and after two levels of experimental manipulation - testosterone implants and immune challenge. Overall, repeatability was significant in both BMR (R=0.25±0.06) and MMR (R=0.52±0.06). Only the testosterone treatment altered the rP between BMR and MMR, which resulted from contrasting effects on rind and re. While rind was high and significant (0.62±0.22) in sham-implanted birds, re was negative and marginally non-significant (-0.15±0.09) in testosterone-treated birds. Thus, the expected mechanistic link between BMR and MMR was apparent, but only in birds with low testosterone levels.

Characteristics of MHC class I genes in house sparrows Passer domesticus as revealed by long cDNA transcripts and amplicon sequencing.

In birds the major histocompatibility complex (MHC) organization differs both among and within orders; chickens Gallus gallus of the order Galliformes have a simple arrangement, while many songbirds of the order Passeriformes have a more complex arrangement with larger numbers of MHC class I and II genes. Chicken MHC genes are found at two independent loci, classical MHC-B and non-classical MHC-Y, whereas non-classical MHC genes are yet to be verified in passerines. Here we characterize MHC class I transcripts (α1 to α3 domain) and perform amplicon sequencing using a next-generation sequencing technique on exon 3 from house sparrow Passer domesticus (a passerine) families. Then we use phylogenetic, selection, and segregation analyses to gain a better understanding of the MHC class I organization. Trees based on the α1 and α2 domain revealed a distinct cluster with short terminal branches for transcripts with a 6-bp deletion. Interestingly, this cluster was not seen in the tree based on the α3 domain. 21 exon 3 sequences were verified in a single individual and the average numbers within an individual were nine and five for sequences with and without a 6-bp deletion, respectively. All individuals had exon 3 sequences with and without a 6-bp deletion. The sequences with a 6-bp deletion have many characteristics in common with non-classical MHC, e.g., highly conserved amino acid positions were substituted compared with the other alleles, low nucleotide diversity and just a single site was subject to positive selection. However, these alleles also have characteristics that suggest they could be classical, e.g., complete linkage and absence of a distinct cluster in a tree based on the α3 domain. Thus, we cannot determine for certain whether or not the alleles with a 6-bp deletion are non-classical based on our present data. Further analyses on segregation patterns of these alleles in combination with dating the 6-bp deletion through MHC characterization across the genus Passer may solve this matter in the future.

Effects of experimentally elevated traffic noise on nestling white-crowned sparrow stress physiology, immune function and life history.

Roads have been associated with behavioral and physiological changes in wildlife. In birds, roads decrease reproductive success and biodiversity and increase physiological stress. Although the consequences of roads on individuals and communities have been well described, the mechanisms through which roads affect birds remain largely unexplored. Here, we examine one mechanism through which roads could affect birds: traffic noise. We exposed nestling mountain white-crowned sparrows (Zonotrichia leucophrys oriantha) to experimentally elevated traffic noise for 5 days during the nestling period. Following exposure to traffic noise we measured nestling stress physiology, immune function, body size, condition and survival. Based on prior studies, we expected the traffic noise treatment to result in elevated stress hormones (glucocorticoids), and declines in immune function, body size, condition and survival. Surprisingly, nestlings exposed to traffic noise had lower glucocorticoid levels and improved condition relative to control nests. These results indicate that traffic noise does affect physiology and development in white-crowned sparrows, but not at all as predicted. Therefore, when evaluating the mechanisms through which roads affect avian populations, other factors (e.g. edge effects, pollution and mechanical vibration) may be more important than traffic noise in explaining elevated nestling stress responses in this species.

Activation of the immune system incurs energetic costs but has no effect on the thermogenic performance of house sparrows during acute cold challenge.

Trade-offs between the immune system and other condition-dependent life-history traits (reproduction, predator avoidance and somatic growth) have been well documented in both birds and mammals. However, no studies have examined the impact of immune activation on thermoregulatory performance during acute cold exposure. Because of their high surface-area-to-volume ratios, small birds incur high energetic costs associated with thermoregulation during cold exposure. Consequently, we predicted that the immune system and the thermoregulatory system would compete for energetic resources. To test this, we immunologically challenged adult house sparrows (Passer domesticus) with 5 mg kg(-1) of lipopolysaccharide (LPS) to induce an acute phase response and measured both resting (RMR; minimum metabolic rate) and summit ( ; maximal metabolic rate during cold exposure) metabolic rates. We found that birds injected with LPS had significantly higher RMR and than birds injected with phosphate-buffered saline, indicating that LPS-treated birds were able to support the cost of both immune activation and thermoregulation under conditions eliciting maximal thermogenic performance. These results suggest that, in the absence of a pathogen, birds that experience short-term activation of the immune system have higher energetic costs during cold exposure, but immune activation does not compromise maximum thermoregulatory performance.

Identification of antibodies against hydropericardium syndrome in wild birds.

1. Domestic fowl and free-living birds were examined for the presence or absence of antibodies against hydropericardium syndrome (HPS) using an indirect haemagglutination assay. 2. Two-hundred and eighty serum samples of commercial (45 broilers, 20 adult layers and 15 Fayoumi fowl) and wild birds, including 65 peafowl, 45 pigeons, 10 crows, 30 house sparrows, 10 doves, 15 ducks, 10 parrots and 15 guinea fowl, were collected and examined. 3. The percentage of HPS-positive serum samples was 80% in house crows, 78% in pigeons, 7% in house sparrows and 6% in peafowl. 4. The sera obtained from parrots, doves, ducks and guinea fowl were all negative. 5. This study suggests that crows and pigeons could be carriers of the HPS agent.

Does immune suppression during stress occur to promote physical performance?

Two adaptationist hypotheses have been proposed to explain why stress, particularly elevation of stress hormones (i.e. glucocorticoids), tends to suppress immune functions. One is that immune suppression represents efforts to minimize autoimmune responses to self-antigens released as organisms cope with stressors (i.e. the autoimmune-avoidance hypothesis). The other is that immune suppression occurs to promote a shunting of resources to life processes more conducive to survival of the stressor (i.e. the re-allocation hypothesis). Here in wild-caught house sparrows (Passer domesticus), we tested the second hypothesis, asking whether sustained elevation of baseline glucocorticoids, due to captivity, caused a greater rate of decline in immune functions than flight performance. A greater decline in immune functions than flight performance would support the re-allocation hypothesis. As in previous studies, we found that captivity tended to alter baseline corticosterone, suggesting that house sparrows experience captivity as a stressor. Captivity also affected several constitutive and induced innate immune metrics: bacterial (Escherichia coli) killing activity of blood and oxidative burst of leukocytes both changed in a manner consistent with immune disregulation. In contrast, breast muscle size and vertical flight (hovering) duration improved over captivity. Collectively, these changes provide indirect support for the re-allocation hypothesis, although within individuals, changes in immune and physical performance were unrelated.

Plasmodium relictum infection and MHC diversity in the house sparrow (Passer domesticus).

Antagonistic coevolution between hosts and parasites has been proposed as a mechanism maintaining genetic diversity in both host and parasite populations. In particular, the high level of genetic diversity usually observed at the major histocompatibility complex (MHC) is generally thought to be maintained by parasite-driven selection. Among the possible ways through which parasites can maintain MHC diversity, diversifying selection has received relatively less attention. This hypothesis is based on the idea that parasites exert spatially variable selection pressures because of heterogeneity in parasite genetic structure, abundance or virulence. Variable selection pressures should select for different host allelic lineages resulting in population-specific associations between MHC alleles and risk of infection. In this study, we took advantage of a large survey of avian malaria in 13 populations of the house sparrow (Passer domesticus) to test this hypothesis. We found that (i) several MHC alleles were either associated with increased or decreased risk to be infected with Plasmodium relictum, (ii) the effects were population specific, and (iii) some alleles had antagonistic effects across populations. Overall, these results support the hypothesis that diversifying selection in space can maintain MHC variation and suggest a pattern of local adaptation where MHC alleles are selected at the local host population level.

An enzootic vector-borne virus is amplified at epizootic levels by an invasive avian host.

Determining the effect of an invasive species on enzootic pathogen dynamics is critical for understanding both human epidemics and wildlife epizootics. Theoretical models suggest that when a naive species enters an established host-parasite system, the new host may either reduce ('dilute') or increase ('spillback') pathogen transmission to native hosts. There are few empirical data to evaluate these possibilities, especially for animal pathogens. Buggy Creek virus (BCRV) is an arthropod-borne alphavirus that is enzootically transmitted by the swallow bug (Oeciacus vicarius) to colonially nesting cliff swallows (Petrochelidon pyrrhonota). In western Nebraska, introduced house sparrows (Passer domesticus) invaded cliff swallow colonies approximately 40 years ago and were exposed to BCRV. We evaluated how the addition of house sparrows to this host-parasite system affected the prevalence and amplification of a bird-associated BCRV lineage. The infection prevalence in house sparrows was eight times that of cliff swallows. Nestling house sparrows in mixed-species colonies were significantly less likely to be infected than sparrows in single-species colonies. Infected house sparrows circulated BCRV at higher viraemia titres than cliff swallows. BCRV detected in bug vectors at a site was positively associated with virus prevalence in house sparrows but not with virus prevalence in cliff swallows. The addition of a highly susceptible invasive host species has led to perennial BCRV epizootics at cliff swallow colony sites. The native cliff swallow host confers a dilution advantage to invasive sparrow hosts in mixed colonies, while at the same sites house sparrows may increase the likelihood that swallows become infected.

Captivity induces hyper-inflammation in the house sparrow (Passer domesticus).

Some species thrive in captivity but others exhibit extensive psychological and physiological deficits, which can be a challenge to animal husbandry and conservation as well as wild immunology. Here, we investigated whether captivity duration impacted the regulation of a key innate immune response, inflammation, of a common wild bird species, the house sparrow (Passer domesticus). Inflammation is one of the most commonly induced and fast-acting immune responses animals mount upon exposure to a parasite. However, attenuation and resolution of inflammatory responses are partly coordinated by glucocorticoid hormones, hormones that can be disregulated in captivity. Here, we tested whether captivity duration alters corticosterone regulation and hence the inflammatory response by comparing the following responses to lipopolysaccharide (LPS; a Gram-negative bacteria component that induces inflammation) of birds caught wild and injected immediately versus those held for 2 or 4 weeks in standard conditions: (1) the magnitude of leukocyte immune gene expression [the cytokines, interleukin 1ß and interleukin 6, and Toll-like receptor 4 (TLR4)], (2) the rate of clearance of endotoxin, and (3) the release of corticosterone (CORT) in response to endotoxin (LPS). We predicted that captivity duration would increase baseline CORT and thus suppress gene expression and endotoxin clearance rate. However, our predictions were not supported: TLR4 expression increased with time in captivity irrespective of LPS, and cytokine expression to LPS was stronger the longer birds remained captive. Baseline CORT was not affected by captivity duration, but CORT release post-LPS occurred only in wild birds. Lastly, sparrows held captive for 4 weeks maintained significantly higher levels of circulating endotoxin than other groups, perhaps due to leakage of microbes from the gut, but exogenous LPS did not increase circulating levels over the time scale samples were collected. Altogether, captivity appears to have induced a hyper-inflammatory state in house sparrows, perhaps due to disregulation of glucocorticoids, natural microflora or both.