Phenotypic and functional analysis of bovine peripheral blood dendritic before parturition by a novel purification methods

Dendritic cells (DCs) are specialized antigen presenting cells specializing in antigen uptake and processing, and play an important role in the innate and adaptive immune response. A subset of bovine peripheral blood DCs was identified as CD172a+/CD11c+/MHC (major histocompatibility complex) class II+ cells. Although DCs are identified at 0.1%?0.7% of peripheral blood mononuclear cells (PBMC), the phenotype and function of DCs remain poorly understood with regard to maintaining tolerance during the pregnancy. All cattle used in this study were 1 month before parturition. We have established a novel method for the purification of DCs from PBMC using magnetic?activated cell sorting, and purified the CD172a+/CD11c+ DCs, with high expression of MHC class II and CD40, at 84.8% purity. There were individual differences in the expressions of CD205 and co?stimulatory molecules CD80 and CD86 on DCs. There were positive correlations between expression of cytokine and co?stimulatory molecules in DCs, and the DCs maintained their immune tolerance, evidenced by their low expressions of the co?stimulatory molecules and cytokine production. These results suggest that before parturition a half of DCs may be immature and tend to maintain tolerance based on the low cytokine production, and the other DCs with high co?stimulatory molecules may already have the ability of modulating the T?cell linagepublishersversionPeer reviewe

COVID‐19: Recovery from Chemosensory Dysfunction. A Multicentre study on Smell and Taste

Objective/Hypothesis With the COVID-19 pandemic, chemosensory dysfunction are among the most prevalent symptoms. Most reports are subjective evaluations, which have been suggested to be unreliable. The objective is to test chemosensory dysfunction and recovery based on extensive psychophysical tests in COVID-19 during the course of the disease. Study Design Prospective cohort study. Methods A total of 111 patients from four centers participated in the study. All tested positive for SARS-COV-2 with RT-PCR. They were tested within 3 days of diagnosis and 28 to 169 days after infection. Testing included extensive olfactory testing with the Sniffin' Sticks test for threshold, discrimination and identification abilities, and with the Taste Sprays and Taste Strips for gustatory function for quasi-threshold and taste identification abilities. Results There was a significant difference in olfactory function during and after infection. During infection 21% were anosmic, 49% hyposmic, and 30% normosmic. After infection only 1% were anosmic, 26% hyposmic, and 73% normosmic. For gustatory function, there was a difference for all taste qualities, but significantly in sour, bitter, and total score. Twenty-six percent had gustatory dysfunction during infection and 6.5% had gustatory dysfunction after infection. Combining all tests 22% had combined olfactory and gustatory dysfunction during infection. After infection no patients had combined dysfunction. Conclusions Chemosensory dysfunction is very common in COVID-19, either as isolated smell or taste dysfunction or a combined dysfunction. Most people regain their chemosensory function within the first 28 days, but a quarter of the patients show persisting dysfunction, which should be referred to specialist smell and taste clinics for rehabilitation of chemosensory function. Level of Evidence 3 Laryngoscope, 202

Evolutionary genetic dissection of human interferons

As revealed by population genetic analyses, different human interferon genes evolved under distinct selective constraints and signatures of positive selection vary according to geographic region, suggesting that some sequence changes may have conferred an advantage by increasing resistance to viral infection

Whole inactivated virus influenza vaccine is superior to subunit vaccine in inducing immune responses and secretion of proinflammatory cytokines by DCs

Background For protection against (re-) infection by influenza virus not only the magnitude of the immune response but also its quality in terms of antibody subclass and T helper profile is important. Information about the type of immune response elicited by vaccination is therefore urgently needed. Objectives The aim of the study was to evaluate in detail the immune response elicited by three current influenza vaccine formulations and to shed light on vaccine characteristics which determine this response. Methods Mice were immunized with whole inactivated virus (WIV), virosomes (VS) or subunit vaccine (SU). Following subsequent infection with live virus, serum antibody titers and Th cell responses were measured. The effects of the vaccines on cytokine production by conventional and plasmacytoid dendritic cells were investigated in vitro. Results and conclusions In Balb/c mice (Th2 prone) as well as in C57Bl/6 mice (Th1 prone), WIV induced consistently higher hemagglutination-inhibition titers and virus-neutralizing antibody titers than VS or SU. In contrast to VS and SU, WIV stimulated the production of the antibody subclasses IgG2a (Balb/c) and IgG2c (C57BL/6), considered to be particularly important for viral clearance, and activation of IFN-gamma-producing T cells. Similar to live virus, WIV stimulated the production of proinflammatory cytokines by conventional dendritic cells and IFN-alpha by plasmacytoid cells, while VS and SU had little effect on cytokine synthesis by either cell type. We conclude that vaccination with WIV in contrast to VS or SU results in the desired Th1 response presumably by induction of type I interferon and other proinflammatory cytokines

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

The administration route is decisive for the ability of the vaccine adjuvant CAF09 to induce antigen-specific CD8+ T-cell responses:the immunological consequences of the biodistribution profile

A prerequisite for vaccine-mediated induction of CD8+ T-cell responses is the targeting of dendritic cell (DC) subsets specifically capable of cross-presenting antigen epitopes to CD8+ T cells. Administration of a number of cationic adjuvants via the intraperitoneal (i.p.) route has been shown to result in strong CD8+ T-cell responses, whereas immunization via e.g. the intramuscular (i.m.) or subcutaneous (s.c.) routes often stimulate weak CD8+ T-cell responses. The hypothesis for this is that self-drainage of the adjuvant/antigen to the lymphoid organs, which takes place upon i.p. immunization, is required for the subsequent activation of cross-presenting lymphoid organ-resident CD8α+ DCs. In contrast, s.c. or i.m. immunization usually results in the formation of a depot at the site of injection (SOI), which hinders the self-drainage and targeting of the vaccine to cross-presenting CD8α+ DCs. We investigated this hypothesis by correlating the biodistribution pattern and the adjuvanticity of the strong CD8+ T-cell inducing liposomal cationic adjuvant formulation 09 (CAF09), which is composed of dimethyldioctadecylammonium bromide/monomycoloyl glycerol liposomes with polyinosinic:polycytidylic acid electrostatically adsorbed to the surface. Biodistribution studies with radiolabeled CAF09 and a surface-adsorbed model antigen [ovalbumin (OVA)] showed that a significantly larger fraction of the vaccine dose localized in the draining lymph nodes (dLNs) and the spleen 6 h after i.p. immunization, as compared to after i.m. immunization. Studies with fluorescently labelled OVA + CAF09 demonstrated a preferential association of OVA + CAF09 to DCs/monocytes, as compared to macrophages and B cells, following i.p. immunization. Administration of OVA + CAF09 via the i.p. route did also result in DC activation, whereas no DC activation could be measured within the same period with unadjuvanted OVA and OVA + CAF09 administered via the s.c. or i.m. routes. In the dLNs, the highest level of activated, cross-presenting CD8α+ DCs was detected at 24 h post immunization, whereas an influx of activated, migrating and cross-presenting CD103+ DCs to the dLNs could be measured after 48 h. This suggests that the CD8α+ DCs are activated by self-draining OVA + CAF09 in the lymphoid organs, whereas the CD103+ DCs are stimulated by the OVA + CAF09 at the SOI. These results support the hypothesis that the self-drainage of OVA + CAF09 to the draining LNs is required for the activation of CD8α+ DCs, while the migratory CD103+ DCs may play a role in sustaining the subsequent induction of strong CD8+ T-cell responses