Surfactant protein (SP) D functions as a soluble pattern recognition molecule to mediate the clearance of pathogens by phagocytes in the innate immune response. We hypothesize that SP-D may also interact with dendritic cells, the most potent antigen presenting cell, to enhance uptake and presentation of bacterial antigens. Using mouse bone marrow-derived dendritic cells, we show that SP-D binds to immature dendritic cells in a dose-, carbohydrate-, and calcium-dependent manner, whereas SP-D binding to mature dendritic cells is reduced. SP-D also binds to Escherichia coli HB101 and enhances its association with dendritic cells. Additionally, SP-D enhances the antigen presentation of an ovalbumin fusion protein expressed in E. coli HB101 to ovalbumin-specific major histocompatibility complex class II T cell hybridomas. The enhancement of antigen presentation by SP-D is dose dependent and is not shared by other collectin-like proteins tested. These studies demonstrate that SP-D augments antigen presentation by dendritic cells and suggest that innate immune molecules such as SP-D may help initiate an adaptive immune response for the purpose of resolving an infection. antigen presenting cell; innate immune response; adaptive immune response; phagocytosis; lung Address for reprint requests and other correspondence: J. R.

The effect of breed and diet on insulin response to glucose challenge and its relation to intramuscular fat deposition was determined in 36 steers with 12 each of greater than 87% Wagyu (referred to as Wagyu), Wagyu x Limousin, and Limousin breeds. Weaned steers were blocked by weight into heavy, medium, and light calves and placed in six pens with two pens per weight type and with two steers of each breed per pen. Three pens with steers from each weightclass were fed backgrounding and finishing diets for 259 d, while the other three pens were fed the same diets where 6% of the barley grain was replaced with sunflower oil. Prior to initiation of the finishing phase of the study the intravenous glucose tolerance test (VGTIT) was conducted in all steers. Once steers were judged as carrying adequate 12th-rib fat, based on weight and days on feed, they were harvested and graded and samples of the longissimus muscle were procured for determination of fat content and fatty acid composition. Dietary oil improved (P = 0.011; 0.06) ADG and feed conversion efficiency of steers during the latter part of backgrounding and only ADG during early part ofthe finishing period. Generally percent kidney, pelvic, and heart fat was the only adiposity assessment increased (P = 0.003) by dietary oil. The IVGTT results indicated that insulin response to intravenous glucose was lower in Limousin steers than in Wagyu steers. Dietary oil decreased (P = 0.052) fasting plasma insulin concentration in Wagyu steers compared with Limousin steers. The correlation coefficients among the IVGTT measures and intramuscular fat content or marbling score were less than 0.4, and only a negative trend existed between fasting insulin and USDA marbling scores. However, the carcasses of the Wagyu steers graded US Choice, and 66% of the Wagyu carcasses graded US Prime, which were substantially better than the quality grades obtained for the carcasses from the other breed types. Dietary oil did not affect muscle fat content but increased (P = 0.01) conjugated linoleic acid (CLA) concentrations by 339%. Results indicated that IVGTT measures were not appropriate indices of marbling potential in cattle and that dietary oil can enhance CLA content of beef.

BackgroundThe new types of mRNA-containing lipid nanoparticle vaccines BNT162b2 and mRNA-1273 and the adenovirus-based vaccine AZD1222 were developed against SARS-CoV-2 and code for its spike (S) protein. Several studies have investigated short-term antibody (Ab) responses after vaccination.ObjectiveHowever, the impact of these new vaccine formats with unclear effects on the long-term Ab response – including isotype, subclass, and their type of Fc glycosylation – is less explored.MethodsHere, we analyzed anti-S Ab responses in blood serum and the saliva of SARS-CoV-2 naïve and non-hospitalized pre-infected subjects upon two vaccinations with different mRNA- and adenovirus-based vaccine combinations up to day 270.ResultsWe show that the initially high mRNA vaccine-induced blood and salivary anti-S IgG levels, particularly IgG1, markedly decrease over time and approach the lower levels induced with the adenovirus-based vaccine. All three vaccines induced, contrary to the short-term anti-S IgG1 response with high sialylation and galactosylation levels, a long-term anti-S IgG1 response that was characterized by low sialylation and galactosylation with the latter being even below the corresponding total IgG1 galactosylation level. Instead, the mRNA, but not the adenovirus-based vaccines induced long-term IgG4 responses – the IgG subclass with inhibitory effector functions. Furthermore, salivary anti-S IgA levels were lower and decreased faster in naïve as compared to pre-infected vaccinees. Predictively, age correlated with lower long-term anti-S IgG titers for the mRNA vaccines. Furthermore, higher total IgG1 galactosylation, sialylation, and bisection levels correlated with higher long-term anti-S IgG1 sialylation, galactosylation, and bisection levels, respectively, for all vaccine combinations.ConclusionIn summary, the study suggests a comparable “adjuvant” potential of the newly developed vaccines on the anti-S IgG Fc glycosylation, as reflected in relatively low long-term anti-S IgG1 galactosylation levels generated by the long-lived plasma cell pool, whose induction might be driven by a recently described TH1-driven B cell response for all three vaccines. Instead, repeated immunization of naïve individuals with the mRNA vaccines increased the proportion of the IgG4 subclass over time which might influence the long-term Ab effector functions. Taken together, these data shed light on these novel vaccine formats and might have potential implications for their long-term efficacy.

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Coronavirus disease 2019 (COVID-19) is a viral infection affecting multiple organ systems of great significance for metabolic processes. Thus, there is increasing interest in metabolic and lipoprotein signatures of the disease, and early analyses have demonstrated a metabolic pattern typical for atherosclerotic and hepatic damage in COVID-19 patients. However, it remains unclear whether this is specific for COVID-19 and whether the observed signature is caused by the disease or rather represents an underlying risk factor. To answer this question, we have analyzed 482 serum samples using nuclear magnetic resonance metabolomics, including longitudinally collected samples from 12 COVID-19 and 20 cardiogenic shock intensive care patients, samples from 18 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody-positive individuals, and single time point samples from 58 healthy controls. COVID-19 patients showed a distinct metabolic serum profile, including changes typical for severe dyslipidemia and a deeply altered metabolic status compared with healthy controls. Specifically, very-low-density lipoprotein and intermediate-density lipoprotein particles and associated apolipoprotein B and intermediate-density lipoprotein cholesterol were significantly increased, whereas cholesterol and apolipoprotein A2 were decreased. Moreover, a similarly perturbed profile was apparent when compared with other patients with cardiogenic shock who are in the intensive care unit when looking at a 1-week time course, highlighting close links between COVID-19 and lipid metabolism. The metabolic profile of COVID-19 patients distinguishes those from healthy controls and also from patients with cardiogenic shock. In contrast, anti-SARS-CoV-2 antibody-positive individuals without acute COVID-19 did not show a significantly perturbed metabolic profile compared with age- and sex-matched healthy controls, but SARS-CoV-2 antibody-titers correlated significantly with metabolic parameters, including levels of glycine, ApoA2, and small-sized low- and high-density lipoprotein subfractions. Our data suggest that COVID-19 is associated with dyslipidemia, which is not observed in anti-SARS-CoV-2 antibody-positive individuals who have not developed severe courses of the disease. This suggests that lipoprotein profiles may represent a confounding risk factor for COVID-19 with potential for patient stratification.