Classical pathway serum complement activity throughout various stages of the annual cycle of a mammalian hibernator, the golden-mantled ground squirrel, Spermophilus lateralis (original) (raw)
Related papers
American Journal of …, 2002
Golden-mantled ground squirrels (Spermophilus lateralis) undergo seasonal hibernation during which core body temperature (Tb) values are maintained 1-2°C above ambient temperature. Hibernation is not continuous. Squirrels arouse at ϳ7-day intervals, during which Tb increases to 37°C for ϳ16 h; thereafter, they return to hibernation and sustain low Tbs until the next arousal. Over the course of the hibernation season, arousals consume 60-80% of a squirrel's winter energy budget, but their functional significance is unknown and disputed. Host-defense mechanisms appear to be downregulated during the hibernation season and preclude normal immune responses. These experiments assessed immune function during hibernation and subsequent periodic arousals. The acute-phase response to bacterial lipopolysaccharide (LPS) was arrested during hibernation and fully restored on arousal to normothermia. LPS injection (ip) resulted in a 1-1.5°C fever in normothermic animals that was sustained for Ͼ8 h. LPS was without effect in hibernating squirrels, neither inducing fever nor provoking arousal, but a fever did develop several days later, when squirrels next aroused from hibernation; the duration of this arousal was increased sixfold above baseline values. Intracerebroventricular infusions of prostaglandin E2 provoked arousal from hibernation and induced fever, suggesting that neural signaling pathways that mediate febrile responses are functional during hibernation. Periodic arousals may activate a dormant immune system, which can then combat pathogens that may have been introduced immediately before or during hibernation. circannual rhythms; Spermophilus lateralis; neural-immune interactions MAINTENANCE OF IMMUNE FUNCTION requires considerable energy expenditure (42, 62) and may limit or constrain the extent to which animals engage in other energetically demanding activities . Large seasonal
International Journal of Medical Sciences, 2000
Background: Hibernation involves periods of severely depressed metabolism (torpor) and decreases in body temperature (Tb). Small arctic mammals (<5kg), in which Tb generally drop drastically, display leukopenia during hibernation. This raised the question of whether the decreased leukocyte counts in mammalian hibernators is due to torpor per se or is secondary to low Tb. The present study examined immune cell counts in brown bears (Ursus arctos), where torpor is only associated with shallow decreases in Tb. The results were compared across hibernator species for which immune and Tb data were available. Methods and Results: The white blood cell counts were determined by flow cytometry in 13 bears captured in the field both during summer and winter over 2 years time. Tb dropped from 39.6±0.8 to 33.5±1.1°C during hibernation. Blood neutrophils and monocytes were lower during hibernation than during the active period (47%, p= 0.001; 43%, p=0.039, respectively), whereas no change in lymphocyte counts was detected (p=0.599). Further, combining our data and those from 10 studies on 9 hibernating species suggested that the decline in Tb explained the decrease in innate immune cells (R 2 =0.83, p<0.0001). Conclusions: Bears have fewer innate immune cells in circulation during hibernation, which may represent a suppressed innate immune system. Across species comparison suggests that, both in small and large hibernators, Tb is the main driver of immune function regulation during winter dormancy. The lack of a difference in lymphocyte counts in this context requires further investigations.
Circadian Clock and Complement Immune System—Complementary Control of Physiology and Pathology?
Frontiers in Cellular and Infection Microbiology, 2020
Mammalian species contain an internal circadian (i.e., 24-h) clock that is synchronized to the day and night cycles. Large epidemiological studies, which are supported by carefully controlled studies in numerous species, support the idea that chronic disruption of our circadian cycles results in a number of health issues, including obesity and diabetes, defective immune response, and cancer. Here we focus specifically on the role of the complement immune system and its relationship to the internal circadian clock system. While still an incompletely understood area, there is evidence that dysregulated proinflammatory cytokines, complement factors, and oxidative stress can be induced by circadian disruption and that these may feed back into the oscillator at the level of circadian gene regulation. Such a feedback cycle may contribute to impaired host immune response against pathogenic insults. The complement immune system including its activated anaphylatoxins, C3a and C5a, not only facilitate innate and adaptive immune response in chemotaxis and phagocytosis, but they can also amplify chronic inflammation in the host organism. Consequent development of autoimmune disorders, and metabolic diseases associated with additional environmental insults that activate complement can in severe cases, lead to accelerated tissue dysfunction, fibrosis, and ultimately organ failure. Because several promising complement-targeted therapeutics to block uncontrolled complement activation and treat autoimmune diseases are in various phases of clinical trials, understanding fully the circadian properties of the complement system, and the reciprocal regulation by these two systems could greatly improve patient treatment in the long term.
PLoS ONE, 2011
White-nose syndrome (WNS) is the most devastating condition ever reported for hibernating bats, causing widespread mortality in the northeastern United States. The syndrome is characterized by cutaneous lesions caused by a recently identified psychrophilic and keratinophylic fungus (Geomyces destructans), depleted fat reserves, atypical behavior, and damage to wings; however, the proximate cause of mortality is still uncertain. To assess relative levels of immunocompetence in bats hibernating in WNS-affected sites compared with levels in unaffected bats, we describe blood plasma complement protein activity in hibernating little brown myotis (Myotis lucifugus) based on microbicidal competence assays using Escherichia coli, Staphylococcus aureus and Candida albicans. Blood plasma from bats collected during mid-hibernation at WNS-affected sites had higher bactericidal ability against E. coli and S. aureus, but lower fungicidal ability against C. albicans when compared with blood plasma from bats collected at unaffected sites. Within affected sites during mid-hibernation, we observed no difference in microbicidal ability between bats displaying obvious fungal infections compared to those without. Bactericidal ability against E. coli decreased significantly as hibernation progressed in bats collected from an affected site. Bactericidal ability against E. coli and fungicidal ability against C. albicans were positively correlated with body mass index (BMI) during late hibernation. We also compared complement activity against the three microbes within individuals and found that the ability of blood plasma from hibernating M. lucifugus to lyse microbial cells differed as follows: E. coli.S. aureus.C. albicans. Overall, bats affected by WNS experience both relatively elevated and reduced innate immune responses depending on the microbe tested, although the cause of observed immunological changes remains unknown. Additionally, considerable trade-offs may exist between energy conservation and immunological responses. Relationships between immune activity and torpor, including associated energy expenditure, are likely critical components in the development of WNS.
Molecular and cellular biochemistry, 1999
Heat shock protein 70 (HSP70) gene expression was studied in a seasonal hibernator, the diurnal ground squirrel, Spermophilus lateralis. RNA transcripts of 2.7 and 2.9 kb hybridizing to an HSP70 cDNA were expressed in both brain and peripheral tissues of pre-hibernation euthermic animals; higher levels of expression were observed during the day than during nighttime samples. A decline in the expression of both transcripts occurred in all tissues examined during hibernation that remained low throughout the hibernation season, including the interbout euthermic periods and regardless of time of day. Quantitative comparisons showed pre-hibernation nighttime HSP70 expression to be as low as that observed during hibernation, despite the drastic increase in metabolic state and nearly 30 degrees C difference in body temperature. In contrast to HSP70, some mRNAs, such as beta-actin and HSP60, remained relatively constant, while others, such as glyceraldehyde 3-phosphate dehydrogenase, increa...
Seasonal changes in the intestinal immune system of hibernating ground squirrels
Developmental & Comparative Immunology, 2007
Hibernation is associated with a prolonged fast (5-8 mo) which has the potential to affect intestinal immunity. We examined several aspects of the intestinal immune system in summer (non-hibernating) and hibernating ground squirrels. Peyer's patches were largely unaffected by hibernation, but numbers of intraepithelial lymphocytes (IEL) and lamina propria leukocytes (LPL) were greater in hibernators compared with summer. Hibernator IEL were less mature as demonstrated by low numbers of cells expressing activation-associated markers and co-receptors. Compared with summer, the percentage of B cells was higher and percentage of T cells was lower in the hibernator LPL. Hibernation was associated with greater mucosal levels of IFN-g, TNF-a, IL-10 and IL-4, but IL-6 and TGF-b were unchanged. Mucosal IgA levels were greater in entrance and torpid hibernators compared with summer. The results suggest that modifications of the intestinal immune system during hibernation may help preserve gut integrity throughout the winter fast. r
Archives of Biochemistry and Biophysics, 2002
The translation state of differentially expressed mRNAs were compared in kidney and brown adipose tissue of the hibernating ground squirrel, Spermophilus tridecemlineatus. Polysome analysis revealed a striking disaggregation of polyribosomes during hibernation and the redistribution of Cox4 (cytochrome c oxidase subunit 4) and Oct2 (organic cation transporter type 2) transcripts into monosome and mRNP fractions of kidney cytoplasmic extracts. Additionally, OCT2 protein levels decreased in kidney of hibernating animals in line with a strong decrease (85%) in translation rate compared with euthermic kidney. There was no translational depression in brown adipose tissue during hibernation and the H isoform of fatty-acid-binding protein (H-FABP), that is up-regulated during hibernation, was increasingly abundant in the heavy polyribosome fraction isolated from the brown adipose of hibernators. This may indicate the existence of a tissue-specific mechanism for the translational control of a subset of genes that are physiologically relevant to the survival of hibernation. Ó