Aged Beagle dogs have decreased neutrophil phagocytosis and neutrophil-related gene expression compared to younger dogs

Hall, Jean A.; Chinn, Rachel M.; Vorachek, William R.; Gorman, M. Elena; Jewell, Dennis E.

doi:10.1016/j.vetimm.2010.05.002

Cited by 21 publications

(16 citation statements)

References 25 publications

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“…This feature is likely related to the high homology between Luk-I and LukED (Spaan et al, 2017 ). Interestingly, this receptor, found both in humans and dogs, also shares a high homology (75%) (Hall et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Understanding the Virulence of Staphylococcus pseudintermedius: A Major Role of Pore-Forming Toxins

Maali¹,

Badiou²,

Martins-Simões³

et al. 2018

Front. Cell. Infect. Microbiol.

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Staphylococcus pseudintermedius is responsible for severe and necrotizing infections in humans and dogs. Contrary to S. aureus, the pathophysiological mechanisms involved in this virulence are incompletely understood. We previously showed the intracellular cytotoxicity induced after internalization of S. pseudintermedius. Herein, we aimed to identify the virulence factors responsible for this cytotoxic activity. After addition of filtered S. pseudintermedius supernatants in culture cell media, MG63 cells, used as representative of non-professional phagocytic cells (NPPc), released a high level of LDH, indicating that the cytotoxicity was mainly mediated by secreted factors. Accordingly, we focused our attention on S. pseudintermedius toxins. In silico analysis found the presence of two PSMs (δ-toxin and PSMε) as well as Luk-I leukotoxin, the presence of which was confirmed by PCR in all clinical strains tested (n = 17). Recombinant Luk-I leukotoxin had no cytotoxic activity on NPPc but the ectopic expression of the CXCR2 receptor in U937 cells conferred cytotoxity to Luk-I. This is in agreement with the lack of Luk-I effect on NPPc and the previous report of Luk-I cytoxic activity on immune cells. Contrary to Luk-I, synthetic δ-toxin and PSMε had a strong cytotoxic activity on NPPc. The secretion of δ-toxin and PSMε at cytotoxic concentrations by S. pseudintermedius in culture supernatant was confirmed by HPLC-MS. In addition, the supplementation of such supernatants with human serum, known to inhibit PSM, induced a complete abolition of cytotoxicity which indicates that PSMs are the key players in the cytotoxic phenotype of NPPc. The results suggest that the severity of S. pseudintermedius infections is, at least in part, explained by a combined action of Luk-I that specifically targets immune cells expressing the CXCR2 receptor, and PSMs that disrupt cell membranes whatever the cell types. The present study strengthens the key role of PSMs in virulence of the different species belonging to Staphylococcus genus.

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Section: Discussionmentioning

confidence: 99%

Understanding the Virulence of Staphylococcus pseudintermedius: A Major Role of Pore-Forming Toxins

Maali¹,

Badiou²,

Martins-Simões³

et al. 2018

Front. Cell. Infect. Microbiol.

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“…Se supplementation delayed the age-associated decline in neutrophil killing ability, as ewes receiving Se had similar killing percentages as non supplemented ewes that were one age category younger. We have previously shown in aged Beagle dogs that older dogs have a significant decrease in neutrophil bacterial killing and, in addition, have lower levels of mRNA for neutrophil-related gene expression compared with younger dogs, including mRNA for myeloperoxidase [41], which may contribute to increased morbidity and mortality with aging. These results are consistent with our finding in this study that older ewes had a higher FR severity and prevalence.…”

Section: Discussionmentioning

confidence: 99%

Selenium Supplementation Restores Innate and Humoral Immune Responses in Footrot-Affected Sheep

et al. 2013

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Dietary selenium (Se) alters whole-blood Se concentrations in sheep, dependent upon Se source and dosage administered, but little is known about effects on immune function. We used footrot (FR) as a disease model to test the effects of supranutritional Se supplementation on immune function. To determine the effect of Se-source (organic Se-yeast, inorganic Na-selenite or Na-selenate) and Se-dosage (1, 3, 5 times FDA-permitted level) on FR severity, 120 ewes with and 120 ewes without FR were drenched weekly for 62 weeks with different Se sources and dosages (30 ewes/treatment group). Innate immunity was evaluated after 62 weeks of supplementation by measuring neutrophil bacterial killing ability. Adaptive immune function was evaluated by immunizing sheep with keyhole limpet hemocyanin (KLH). The antibody titer and delayed-type hypersensitivity skin test to KLH were used to assess humoral immunity and cell-mediated immunity, respectively. At baseline, FR-affected ewes had lower whole-blood and serum-Se concentrations; this difference was not observed after Se supplementation. Se supplementation increased neutrophil bacterial killing percentages in FR-affected sheep to percentages observed in supplemented and non-supplemented healthy sheep. Similarly, Se supplementation increased KLH antibody titers in FR-affected sheep to titers observed in healthy sheep. FR-affected sheep demonstrated suppressed cell-mediated immunity at 24 hours after intradermal KLH challenge, although there was no improvement with Se supplementation. We did not consistently prevent nor improve recovery from FR over the 62 week Se-treatment period. In conclusion, Se supplementation does not prevent FR, but does restore innate and humoral immune functions negatively affected by FR.

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“…In a study in beagles, the concentrations of peripheral T lymphocytes, T cytotoxic lymphocytes, and B lymphocytes were lower in older dogs ( > 10 years) than in mature adult dogs (4 years old) [26]. Aged beagle dogs have decreased neutrophil phagocytosis when compared with young dogs, as assessed by their ability to phagocytize Lactococcus lactis ex vivo [27]. In the same study, younger dogs had significantly higher levels of mRNA for IL8R, L-selectin, and interleukin-1β-converting enzyme.…”

Section: Immune Functionmentioning

confidence: 97%

The beneficial role of anti-inflammatory dietary ingredients in attenuating markers of chronic low-grade inflammation in aging

Panickar¹,

Jewell²

2015

Hormone Molecular Biology and Clinical Investigation

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Aging in humans is associated with chronic low-grade inflammation (systemic), and this condition is sometimes referred to as "inflammaging". In general, canines also age similarly to humans, and such aging is associated with a decline in mobility, joint problems, weakened muscles and bones, reduced lean body mass, cancer, increased dermatological problems, decline in cognitive ability, reduced energy, decreased immune function, decreased renal function, and urinary incontinence. Each of these conditions is also associated with an increase in pro-inflammatory cytokines. An inflammatory state characterized by an increase in pro-inflammatory markers including but not restricted to tumor necrosis factor-α, interleukin-6, IL-1β, and C-reactive protein (CRP) is believed to contribute to or worsen a general decline in biological mechanisms responsible for physical function with aging. Nutritional management of inflammation in aging dogs is important in maintaining health. In particular, natural botanicals have bioactive components that appear to have robust anti-inflammatory effects and, when included in the diet, may contribute to a reduction in inflammation. While there are scientific data to support the anti-inflammatory effects and the efficacy of such bioactive molecules from botanicals, the clinical data are limited and more studies are needed to validate the efficacy of these ingredients. This review will summarize the role of dietary ingredients in reducing inflammatory molecules as well as review the evidence available to support the role of diet and nutrition in reducing chronic low-grade systemic inflammation in animal and human studies with a special reference to canines, where possible.

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Aged Beagle dogs have decreased neutrophil phagocytosis and neutrophil-related gene expression compared to younger dogs

Cited by 21 publications

References 25 publications

Understanding the Virulence of Staphylococcus pseudintermedius: A Major Role of Pore-Forming Toxins

Understanding the Virulence of Staphylococcus pseudintermedius: A Major Role of Pore-Forming Toxins

Selenium Supplementation Restores Innate and Humoral Immune Responses in Footrot-Affected Sheep

The beneficial role of anti-inflammatory dietary ingredients in attenuating markers of chronic low-grade inflammation in aging

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