An official website of the United States government
Abstract GenX is an environmental contaminant with wide industrial use and found in drinking water. These chemicals have high bioaccumulation and cause adverse health effects in animals and humans. Previous study has shown that pre GenX perfluoroalkyl/polyfluoroalkyl substances (PFAS) and GenX affect immune cells but there is limited study on their impact on innate immune cells (neutrophils) in livestock, such as cows. This study evaluated the effect of GenX exposure on innate and adaptive immune response gene transcription in bovine neutrophils ex vivo. Whole blood was collected using Acid citrate dextrose as a coagulant from cows (n = 5). Neutrophils were isolated using differential centrifugation and hypotonic lysis of red cells. Isolated neutrophils were treated with GenX (100 ng), or untreated (control group) for hour at 37oC, 5%CO2 and 85% relative humidity. After treatment, total RNA was extracted using Trizol reagent, reverse transcribed to cDNA, and quantitative PCR was performed using the innate and adaptive immunity RT2 profiler array (Qiagen) with 84 genes. The qPCR data were analyzed using Livak’s method to calculate fold change (FC) in gene expression between GenX-treated and control neutrophils, and FC >2, (p < 0.05) was considered significant. Normalization of data was performed with GAPDH and Beta Actin as an internal control. Out of the 84 genes tested, 78 were expressed, 25 were upregulated and4 were downregulated, in response to GenX exposure. Exposure to GenX upregulated the expression of TLR8 (FC = 24.75), NOD2 (FC = 7.65), STAT1 (FC = 49.35), HLA-A (FC = 14.07), and NKB1A (FC = 16.52). Treatment with GenX decreased the expression TICAM1 (FC = -2.30), CD86 (FC = -2.27) and RAG1 (FC = -2.50). These results indicate that GenX exposure can activate and modulate the expression of innate and adaptive immune response genes in cow neutrophils. STAT1 is involved in transcriptional regulation and activation of TLR7/8 shifts neutrophil function from phagocytosis to NETosis. Thus, the mechanism of action of GenX on identified gene targets and their function and possible animal health consequences warrants further study.
more »
« less
Dehydration enhances innate immunity in a semiaquatic snake from the wet‐dry tropics
Abstract Dehydration is considered a physiological challenge, and many organisms live in environments that undergo periods of reduced water availability that can lead to dehydration. Recent studies have found a positive relationship between dehydration and innate immune function in animals adapted to xeric or semixeric environments. To explore the generality of this relationship, we examined the impact of dehydration on innate immune performance in water pythons (Liasis fuscus), a semiaquatic snake from the wet‐dry tropics of Australia. We collected blood samples from male and female water pythons held in the laboratory without food and water for 4 weeks. We also collected blood from free‐ranging snakes throughout the Austral dry‐season. We evaluated plasma osmolality and innate immune function (agglutination, lysis, and bacterial‐killing ability) and found that increased osmolality, whether manipulated in the laboratory or as a result of natural water limitation, resulted in enhanced aspects of innate immune performance. Counter‐intuitively, snakes in the wild became more hydrated as the dry season progressed, suggesting the dehydrated snakes move to water sources periodically to rehydrate. Comparing our data with those from previous studies, we suspect species divergence in the level of dehydration (i.e., hyperosmolality) that triggers enhanced immune capabilities.
more »
« less
- Award ID(s):
- 1606367
- PAR ID:
- 10088115
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Experimental Zoology Part A: Ecological and Integrative Physiology
- Volume:
- 331
- Issue:
- 4
- ISSN:
- 2471-5638
- Page Range / eLocation ID:
- p. 245-252
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Neopterin, a product of activated white blood cells, is a marker of nonspecific inflammation that can capture variation in immune investment or disease-related immune activity and can be collected noninvasively in urine. Mounting studies in wildlife point to lifetime patterns in neopterin related to immune development, aging, and certain diseases, but rarely are studies able to assess whether neopterin can capture multiple concurrent dimensions of health and disease in a single system. We assessed the relationship between urinary neopterin stored on filter paper and multiple metrics of health and disease in wild geladas (Theropithecus gelada), primates endemic to the Ethiopian highlands. We tested whether neopterin captures age-related variation in inflammation arising from developing immunity in infancy and chronic inflammation in old age, inflammation related to intramuscular tapeworm infection, helminth-induced anti-inflammatory immunomodulation, and perturbations in the gastrointestinal microbiome. We found that neopterin had a U-shaped relationship with age, no association with larval tapeworm infection, a negative relationship with metrics related to gastrointestinal helminth infection, and a negative relationship with microbial diversity. Together with growing research on neopterin and specific diseases, our results demonstrate that urinary neopterin can be a powerful tool for assessing multiple dimensions of health and disease in wildlife.more » « less
-
Abstract Infectious disease systems frequently exhibit strong seasonal patterns, yet the mechanisms that underpin intra‐annual cycles are unclear, particularly in tropical regions. We hypothesized that host immune function fluctuates seasonally, contributing to oscillations in infection patterns in a tropical disease system. To test this hypothesis, we investigated a key host defense of amphibians against a lethal fungal pathogen,Batrachochytrium dendrobatidis(Bd). We integrated two field experiments in which we perturbed amphibian skin secretions, a critical host immune mechanism, in Panamanian rocket frogs (Colostethus panamansis). We found that this immunosuppressive technique of reducing skin secretions in wild frog populations increasedBdprevalence and infection intensity, indicating that this immune defense contributes to resistance toBdin wild frog populations. We also found that the chemical composition and anti‐Bdeffectiveness of frog skin secretions varied across seasons, with greater pathogen inhibition during the dry season relative to the wet season. These results suggest that the effectiveness of this host defense mechanism shifts across seasons, likely contributing to seasonal infection patterns in a lethal disease system. More broadly, our findings indicate that host immune defenses can fluctuate across seasons, even in tropical regions where temperatures are relatively stable, which advances our understanding of intra‐annual cycles of infectious disease dynamics.more » « less
-
Drosophila immune priming to Enterococcus faecalis relies on immune tolerance rather than resistanceGarsin, Danielle A. (Ed.)Innate immune priming increases an organism’s survival of a second infection after an initial, non-lethal infection. We usedDrosophila melanogasterand an insect-derived strain ofEnterococcus faecalisto study transcriptional control of priming. In contrast to other pathogens, the enhanced survival in primed animals does not correlate with decreasedE.faecalisload. Further analysis shows that primed organisms tolerate, rather than resist infection. Using RNA-seq of immune tissues, we found many genes were upregulated in only primed flies, suggesting a distinct transcriptional program in response to initial and secondary infections. In contrast, few genes continuously express throughout the experiment or more efficiently re-activate upon reinfection. Priming experiments in immune deficient mutants revealed Imd is largely dispensable for responding to a single infection but needed to fully prime. Together, this indicates the fly’s innate immune response is plastic—differing in immune strategy, transcriptional program, and pathway use depending on infection history.more » « less
-
Abstract In semi‐arid regions where drought and wildfire events often co‐occur, such as in Southern California chaparral, relationships between plant hydration, drought‐ and fire‐adapted traits may explain landscape‐scale wildfire dynamics. To examine these patterns, fire scientists and plant physiologists quantify hydration in plants via mass‐based metrics of water content, including live fuel moisture, or pressure‐based metrics of physiological status, such as xylem water potential; however, relationships across these metrics, plant traits and flammability remain unresolved.To determine the impact of hydration on tissue‐level flammability (leaves and stems), we conducted laboratory dehydration tests across wet and dry seasons in which we simultaneously measured xylem water potential, live fuel moisture and flammability. We tested two widespread chaparral shrubs,Adenostoma fasciculatumandCeanothus megacarpus.Live fuel moisture showed a threshold‐type relationship with tissue flammability (increased ignitability and combustibility at specific hydration levels) that aligned with drought‐response traits (turgor loss point) and fire behaviour (increased fire likelihood and spread) identified at the landscape scale. Water potential was the better predictor of flammability in linear statistical models.A. fasciculatumwas more flammable thanC. megacarpus, and both species were more flammable during the wet growing season, suggesting seasonal growth or drought‐related tissue characteristics other than moisture content, such as lignin or chemical content, are critical for determining flammability.Our results suggest a mechanism for landscape‐scale increases in flammability at specific levels of drought stress. Integration of drought‐related traits, such as the turgor loss point, might improve models of wildfire risk in drought‐ and fire‐prone systems. Read the freePlain Language Summaryfor this article on the Journal blog.more » « less
