SummaryApproximately 10% of the patients diagnosed with type 2 diabetes (T2D) have detectable serum levels of glutamic acid decarboxylase 65 autoantibodies (GADA). These patients usually progress to insulin dependency within a few years, and are classified as being latent autoimmune diabetes in adults (LADA). A decrease in the frequency of peripheral blood natural killer (NK) cells has been reported recently in recent-onset T1D and in high-risk individuals prior to the clinical onset. As NK cells in LADA patients have been investigated scarcely, the aim of this study was to use multicolour flow cytometry to define possible deficiencies or abnormalities in the frequency or activation state of NK cells in LADA patients prior to insulin dependency. All patients were GADA-positive and metabolically compensated, but none were insulin-dependent at the time blood samples were taken. LADA patients exhibited a significant decrease in NK cell frequency in peripheral blood compared to healthy individuals (P = 0·0018), as reported previously for recent-onset T1D patients. Interestingly, NKG2D expression was increased significantly (P < 0·0001), whereas killer cell immunoglobulin-like receptor (KIR)3DL1 expression was decreased (P < 0·0001) within the NK cell population. These observations highlight a defect in both frequency and activation status of NK cells in LADA patients and suggest that this immunological alteration may contribute to the development of autoimmune diabetes by affecting peripheral tolerance. Indeed, recent evidence has demonstrated a regulatory function for NK cells in autoimmunity. Moreover, the decrease in NK cell number concords with observations obtained in recent-onset T1D, implying that similar immunological dysfunctions may contribute to the progression of both LADA and T1D.
Yeast such as inactivated Candida utilis produced from lignocellulosic biomass from underutilized wood co-products as a second-generation sugar source is a potentially sustainable protein feed ingredient in diets for piglets. This study aimed to evaluate the effects of C. utilis added to diets for weaned piglets on growth performance and digestive function when replacing main protein sources. Forty-eight piglets weaned at 30 days of age, with a mean starting weight of 11.06 ± 0.84 kg were fed one of four dietary treatments for 28 days: a conventional control diet with soybean meal, fishmeal, rapeseed meal, and potato protein or one of three experimental diets containing 10, 20 or 40% crude protein (CP) from yeast (CU10, CU20, and CU40, respectively). Adding yeast to diets did not affect growth performance compared with the control. The diet with 40% CP from C. utilis had higher apparent total tract digestibility (ATTD) of CP compared with the control (P = 0.034) and higher ATTD of ash (P < 0.001) compared with the control. The ATTD of neutral detergent fiber decreased in the CU40 diet compared with the control (P = 0.006). The apparent ileal digestibility (AID) of ash increased (P = 0.001) in the CU40 diet compared with the control, while the AID of CP and amino acids was unaffected. Villi-height increased in jejunum (P = 0.007) and ileum (P = 0.047), and villus-height: crypt-depth ratio increased (P = 0.001) in jejunum of piglets fed the CU40 diet compared with the control. Fecal dry matter increased linearly with increasing levels of C. utilis in the diets at day 7 after weaning (P = 0.001) and was higher for the CU40 group compared with the control group at day 21 after weaning (P = 0.027). Trypsin activity and messenger RNA expression of nine genes encoding for nutrient transporters in the jejunum did not differ among diets. Collectively, the results indicated that C. utilis can replace 40% of CP from the main protein sources traditionally used in diets for weaned piglets while maintaining growth and improving digestive function.
Rapeseed meal (RSM) is an alternative feed ingredient to soybean meal (SBM) in pig diets. However, knowledge on the effect of RSM on gut health, especially in relation to changes in gut microbiota is still limited. In our study, Norwegian Landrace weaner pigs were fed with either a control diet (CON) based on wheat, barley and SBM, or a high-fiber experimental diet where SBM was replaced by RSM (RSF). We found no large differences in the gut microbiota of pigs fed the two diets, suggesting that RSF does not disturb the gut microbiota and the normal gut function. The relative abundance of SCFA-producing phylotypes and colon-health related phylotypes increased in the large intestine of RSF-fed pigs. Among them, Lachnospira and Coprococcus were negatively associated with the presence of neutrophils in the colon wall. The higher abundance of these bacteria in colon of RSF pigs may suggest an anti-inflammatory stimulus effect of the RSF diet. The gut microbiota of RSF-fed pigs was relatively unaltered following episodes of diarrhea suggesting that the RSF diet may promote robustness in weaner pigs and reduce the risk of dysbiosis.
The dynamics of skin-draining cells following infection or vaccination provide important insight into the initiation of immune responses. In this study, the local recruitment and activation of immune cells in draining lymph nodes (LNs) was studied in calves in an adjuvant-induced inflammation. A transient but remarkably strong recruitment of monocytes was demonstrated after onset of inflammation, constituting up to 41% of live cells in the draining LNs after 24 h. Numerous CD14+ cells were visualized in subcutaneous tissues and draining LNs, and the majority of these cells did not express dendritic cell-associated markers CD205 and CD11c. In the LNs, recruited cells were predominately of a CD14++ and CD16+ phenotype, consistent with an intermediate monocyte subset characterized to possess a high inflammatory potential. Moreover, monocytes from the draining LN showed a high expression of genes coding for pro-inflammatory cytokines, including IL-1β, IL-6, TNFa, and TGFβ. Shortly after their appearance in the LN cortical areas, the monocytes had moved into the medulla followed by an increase in peripheral blood. In conclusion, this study provides novel information on in vivo monocyte recruitment and migration after onset of inflammation.
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