Identification of a porcine liver eomes-high-T-bet-low NK cell subset that resembles human liver resident NK cells

Natural killer (NK) cells are cells of the innate immunity and play an important role in the defense against viral infections and cancer, but also contribute to shaping adaptive immune responses. Long-lived tissue-resident NK cells have been described in man and mouse, particularly in the liver, contributing to the idea that the functional palette of NK cells may be broader than originally thought, and may include memory-like responses and maintaining tissue homeostasis. Remarkably, liver resident (lr)NK cells in man and mouse show substantial species-specific differences, in particular reverse expression patterns of the T-box transcription factors Eomesodermin (Eomes) and T-bet (Eomes(high)T-bet(low) in man and vice versa in mouse). In pig, compared to blood NK cells which are CD3-CD8 alpha(high) cells, the porcine liver contains an abundant additional CD3-CD8 alpha(dim) NK cell subpopulation. In the current study, we show that this porcine CD3-CD8 alpha(dim) liver NK population is highly similar to its human lrNK counterpart and therefore different from mouse lrNK cells. Like human lrNK cells, this porcine NK cell population shows an Eomes(high)T-bet(low) expression pattern. In addition, like its human counterpart, the porcine liver NK population is CD49e(-) and CXCR6(+). Furthermore, the porcine Eomes(high)T-bet(low) liver NK cell population is able to produce IFN-gamma upon IL-2/12/18 stimulation but lacks the ability to kill K562 or pseudorabies virus-infected target cells, although limited degranulation could be observed upon incubation with K562 cells or upon CD16 crosslinking. All together, these results show that porcine Eomes(high)T-bet(low) NK cells in the liver strongly resemble human lrNK cells, and therefore indicate that the pig may represent a unique model to study the function of these lrNK cells in health and disease

Diagnosis of dental problems in pet rabbits (Oryctolagus cuniculus)

Dental problems are very common in pet rabbits. To establish a correct diagnosis of rabbit dental pathology, a general knowledge of normal dental anatomy and physiology is necessary. The specific anatomy and the most common pathologies of rabbit dentition are reviewed. Techniques for diagnosing dental abnormalities - such as clinical examination, radiography and computed tomography (CT) - are summarized. Finally two clinical cases of rabbits with dental pathologies are described

β-glucan-induced IL-10 secretion by monocytes triggers porcine NK cell cytotoxicity

Beta-glucans are naturally occurring polysaccharides present in cell walls of fungi, yeast, bacteria, cereals, seaweed, and algae. These microbe-associated molecular patterns (MAMPs) possess immunomodulatory properties. In human, it has been suggested that NK cells can be activated by β-glucans. Here, we aimed to elucidate whether β-glucans modulate porcine NK cell responses in vitro and if so, how these effects are mediated. We investigated the effect of two β-glucans, Macrogard and Curdlan, which differ in solubility and structure. Direct addition of β-glucans to purified porcine NK cells did not affect cytotoxicity of these cells against K562 target cells. However, when using PBMC instead of purified NK cells, β-glucan addition significantly increased NK cell-mediated cytotoxicity. This effect depended on factors secreted by CD14+ monocytes upon β-glucan priming. Further analysis showed that monocytes secrete TNF-α, IL-6, and IL-10 upon β-glucan addition. Of these, IL-10 turned out to play a critical role in β-glucan-triggered NK cell cytotoxicity, since depletion of IL-10 completely abrogated the β-glucan-induced increase in cytotoxicity. Furthermore, addition of recombinant IL-10 to purified NK cells was sufficient to enhance cytotoxicity. In conclusion, we show that β-glucans trigger IL-10 secretion by porcine monocytes, which in turn leads to increased NK cell cytotoxicity, and thereby identify IL-10 as a potent stimulus of porcine NK cell cytotoxicity

Comparative transcriptomics of porcine liver-resident CD8αdim, liver CD8αhigh and circulating blood CD8αhigh NK cells reveals an intermediate phenotype of liver CD8αhigh NK cells

Liver-resident NK (lrNK) cells have been studied in humans as well as in mice. Unfortunately, important differences have been observed between murine and human lrNK cells, complicating the extrapolation of data obtained in mice to man. We previously described two NK cell subsets in the porcine liver: A CD8αhigh subset, with a phenotype much like conventional CD8αhigh NK cells found in the peripheral blood, and a specific liver-resident CD8αdim subset which phenotypically strongly resembles human lrNK cells. These data suggest that the pig might be an attractive model for studying lrNK cell biology. In the current study, we used RNA-seq to compare the transcriptome of three porcine NK cell populations: Conventional CD8αhigh NK cells from peripheral blood (cNK cells), CD8αhigh NK cells isolated from the liver, and the liver-specific CD8αdim NK cells. We found that highly expressed transcripts in the CD8αdim lrNK cell population mainly include genes associated with the (adaptive) immune response, whereas transcripts associated with cell migration and extravasation are much less expressed in this subset compared to cNK cells. Overall, our data indicate that CD8αdim lrNK cells show an immature and anti-inflammatory phenotype. Interestingly, we also observed that the CD8αhigh NK cell population that is present in the liver appears to represent a population with an intermediate phenotype. Indeed, while the transcriptome of these cells largely overlaps with that of cNK cells, they also express transcripts associated with liver residency, in particular CXCR6. The current, in-depth characterization of the transcriptome of porcine liver NK cell populations provides a basis to use the pig model for research into liver-resident NK cells

Setting the stage : impact of beta-glucans and the liver environment on porcine natural killer cells

Natural killer (NK) cells are typically considered as short-lived innate immune cells, important to eliminate virus-infected and malignant cells. They are also known to steer the adaptive immune response via the production of cytokines such as IFN-γ and TNF-α. More recently, however, additional features of NK cells have been discovered and highlighted, especially in the liver of mouse and man. For example, liver-resident (lr) NK cells are able to mount antigen-specific responses, develop a memory-like phenotype and are long-lived. These recent insights in NK cell biology might open doors towards the application of NK cells in innovative vaccination strategies and novel therapeutics

The intermediate effect of geographic proximity on intergenerational support: A comparison of France and Bulgaria

Background: The geographic proximity of parents and adult children is a key element of intergenerational solidarity. Many studies have identified geographical distance as an important determinant of intergenerational support: living nearby increases the amount of mutual support provided. It can, however, also be regarded as a dimension of intergenerational solidarity: the current degree of proximity is the result of past migration decisions made by both generations, in which present and future care demands potentially played a key role. Objective: We take this endogenous nature of geographical distance into account by examining the indirect effect of the determinants of the actual level of support through geographical distance. Both upward support (personal care provided to mother) and downward support (help with childcare received from mother) are considered. Methods: Path analyses are performed on data from the Generations and Gender Survey for France and Bulgaria using a general latent-variable modelling framework in multiple-group models. Results: In addition to strongly affecting the level of support provided and received, geographical distance itself is affected by several individual and family-related variables, which in turn have an indirect effect on the level of intergenerational support. The results suggest that proximity can be used as an adaptive strategy: e.g., working adult children in France receive more help with childcare because of their greater proximity to their mothers. Having a greater care need may have triggered this choice of residence. Similarly, single parents with no partner to rely on tend to live closer to their mothers, and therefore receive more help. Conclusions: Geographic proximity can be considered a latent form of solidarity that functions as a mediator between background factors and manifest, functional solidarity. © 2012 Leen Heylen et al.status: publishe

The intermediate effect of geographic proximity on intergenerational support : a comparison of France and Bulgaria

BACKGROUND The geographic proximity of parents and adult children is a key element of intergenerational solidarity. Many studies have identified geographical distance as an important determinant of intergenerational support: living nearby increases the amount of mutual support provided. It can, however, also be regarded as a dimension of intergenerational solidarity: the current degree of proximity is the result of past migration decisions made by both generations, in which present and future care demands potentially played a key role. OBJECTIVE We take this endogenous nature of geographical distance into account by examining theindirect effect of the determinants of the actual level of support through geographical distance. Both upward support (personal care provided to mother) and downward support (help with childcare received from mother) are considered. METHODS Path analyses are performed on data from the Generations and Gender Survey for France and Bulgaria using a general latent-variable modelling framework in multiple-group models. RESULTS In addition to strongly affecting the level of support provided and received, geographical distance itself is affected by several individual and family-related variables, which in turn have an indirect effect on the level of intergenerational support. The results suggest that proximity can be used as an adaptive strategy: e.g., working adult children in France receive more help with childcare because of their greater proximity to their mothers. Having a greater care need may have triggered this choice of residence. Similarly, single parents with no partner to rely on tend to live closer to their mothers, and therefore receive more help. CONCLUSIONS Geographic proximity can be considered a latent form of solidarity that functions as a mediator between background factors and manifest, functional solidarity