Sialylation of IgG inhibits the formation of galactose-deficient IgA1-containing immune complexes and protects mesangial cells from injury in IgA nephropathy

Background The addition of sialic acid alters IgG from a pro-inflammatory state to an anti-inflammatory state. However, there is a lack of research on the changes of IgG sialylation in IgA nephropathy (IgAN). Methods This study included a total of 184 IgAN patients. The sialylated IgG (SA-IgG), IgG-galactose-deficient IgA1 complex (IgG-Gd-IgA1-IC), IL-6, TNF-α, and TGF-β were detected using commercial ELISA kits. SA-IgG, non-sialylated IgG (NSA-IgG), sialylated IgG-IgA1 complex (SA-IgG-IgA1), and non-sialylated IgG-IgA1 complex (NSA-IgG-IgA1) were purified from IgAN patients and healthy controls (HCs). Results The mean SA-IgG levels in plasma and B lymphocytes in IgAN patients were significantly higher than those of healthy controls. A positive correlation was found between SA-IgG levels in plasma and B lymphocytes. In vitro, the results showed that the release of IgG-Gd-IgA1-IC was significantly decreased in peripheral blood mononuclear cells (PBMCs) cultured with SA-IgG from both IgAN patients and healthy controls. The proliferation ability and the release of IL-6, TNF-α, and TGF-β in human mesangial cells (HMCs) were measured after stimulating with SA-IgG-IgA1-IC and NSA-IgG-IgA1-IC. The mesangial cell proliferation levels induced by NSA-IgG-IgA1-IC derived from IgAN patients were significantly higher than those caused by SA-IgG-IgA1-IC derived from IgAN patients and healthy controls. Compared with NSA-IgG-IgA1 from healthy controls, IgAN-NSA-IgG-IgA1 could significantly upregulate the expression of IL-6 and TNF-α in mesangial cells. The data showed that there weren’t any significant differences in the levels of IL-6, TNF-α, and TGF-β when treated with IgAN-SA-IgG-IgA1 and HC-NSA-IgG-IgA1. Conclusions The present study demonstrated that the sialylation of IgG increased in patients with IgA nephropathy. It exerted an inhibitory effect on the formation of Gd-IgA1-containing immune complexes in PBMCs and the proliferation and inflammation activation in mesangial cells.

Immunosuppressive Isopimarane Diterpenes From Cultures of the Endophytic Fungus Ilyonectria robusta

Five new isopimarane diterpenes, robustaditerpene A-E (1–5), which include 19-nor-isopimarane skeleton and isopimarane skeleton, were isolated from the liquid fermentation of the endophytic fungus Ilyonectria robusta collected from Bletilla striata. The structure elucidation and relative configuration assignments of all compounds were accomplished by interpretation of NMR and HRESIMS spectrometric analyses and 13C NMR calculation. And the absolute configuration of 1-5 were identified by single-crystal X-ray diffraction and ECD calculation. Compound 3 inhibited lipopolysaccharide-induced B lymphocytes cell proliferation with an IC50 value at 17.42 ± 1.57 μM while compound 5 inhibited concanavalin A-induced T lymphocytes cell proliferation with an IC50 value at 75.22 ± 6.10 μM. These data suggested that compounds 3 and 5 may possess potential immunosuppressive prospect.

Immunophenotype of the inflammatory response in the central and enteric nervous systems of cockatiels (Nymphicus hollandicus) experimentally infected with parrot bornavirus 2

Proventricular dilatation disease is a lethal disease of psittacine birds. In this study, we characterized the local cellular immune response in the brain, proventriculus, and small intestine of 27 cockatiels ( Nymphicus hollandicus) experimentally infected with parrot bornavirus 2 (PaBV-2). Perivascular cuffs in the brain were composed of CD3+ T-lymphocytes and Iba1+ macrophages/microglia in most cockatiels (n = 26). In the ganglia of the proventriculus, CD3+ T-lymphocytes (n = 17) and Iba1+ macrophages (n = 13) prevailed. The ganglia of the small intestine had a more homogeneous distribution of these leukocytes, including PAX5+ B-lymphocytes (n = 9), CD3+ T-lymphocytes (n = 8), and Iba1+ macrophages (n = 8). Our results indicate that perivascular cuffs in the brain and the inflammatory infiltrate in the proventriculus of PaBV-2-infected cockatiels is predominately composed of T-lymphocytes, while the inflammatory infiltrates in the ganglia of the small intestine are characterized by a mixed infiltrate composed of T-lymphocytes, B-lymphocytes, and macrophages.

Trypanosoma cruzi Induces B Cells That Regulate the CD4+ T Cell Response

Trypanosoma cruzi infection induces a polyclonal B cell proliferative response characterized by maturation to plasma cells, excessive generation of germinal centers, and secretion of parasite-unrelated antibodies. Although traditionally reduced to the humoral response, several infectious and non-infectious models revealed that B lymphocytes could regulate and play crucial roles in cellular responses. Here, we analyze the trypomastigote-induced effect on B cells, their effects on CD4+ T cells, and their correlation with in vivo findings. The trypomastigotes were able to induce the proliferation and the production of IL-10 or IL-6 of naïve B cells in co-culture experiments. Also, we found that IL-10-producing B220lo cells were elicited in vivo. We also found up-regulated expression of FasL and PD-L1, proteins involved in apoptosis induction and inhibition of TCR signaling, and of BAFF and APRIL mRNAs, two B-cell growth factors. Interestingly, it was observed that IL-21, which plays a critical role in regulatory B cell differentiation, was significantly increased in B220+/IL-21+ in in vivo infections. This is striking since the secretion of IL-21 is associated with T helper follicular cells. Furthermore, trypomastigote-stimulated B-cell conditioned medium dramatically reduced the proliferation and increased the apoptotic rate on CD3/CD28 activated CD4+ T cells, suggesting the development of effective regulatory B cells. In this condition, CD4+ T cells showed a marked decrease in proliferation and viability with marginal IL-2 or IFNγ secretion, which is counterproductive with an efficient immune response against T. cruzi. Altogether, our results show that B lymphocytes stimulated with trypomastigotes adopt a particular phenotype that exerts a strong regulation of this T cell compartment by inducing apoptosis, arresting cell division, and affecting the developing of a proinflammatory response.

Bacterial meningitis in the practice of a primary care physician. Clinical and immunological efficacy of recombinant interleukin-2 in the complex therapy of bacterial meningitis

The article analyzes the pathogenetic features of bacterial meningitis and substantiates the scheme of complex therapy of the disease using the recombinant cytokine interleukin-2 (IL2). The clinical, immunological and microbiological efficacy of the complex therapy scheme has been revealed. It has been shown that the pleiotropic effects of recombinant IL-2, its effect on the activity of metabolic processes at the cellular and subcellular levels, the ability to stabilize the system of lipid peroxidation of cell membranes, the ability to influence the processes of clonal proliferation and differentiation of T- and B-lymphocytes, make its use justified in complex therapy of meningitis.

Preparation and In Vitro Evaluation of RITUXfab-Decorated Lipoplexes to Improve Delivery of siRNA Targeting C1858T PTPN22 Variant in B Lymphocytes

Autoimmune endocrine disorders, such as type 1 diabetes (T1D) and thyroiditis, at present are treated with only hormone replacement therapy. This emphasizes the need to identify personalized effective immunotherapeutic strategies targeting T and B lymphocytes. Among the genetic variants associated with several autoimmune disorders, the C1858T polymorphism of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, encoding for Lyp variant R620W, affects the innate and adaptive immunity. We previously exploited a novel personalized immunotherapeutic approach based on siRNA delivered by liposomes (lipoplexes) that selectively inhibit variant allele expression. In this manuscript, we improved lipoplexes carrying siRNA for variant C1858T by functionalizing them with Fab of Rituximab antibody (RituxFab-Lipoplex) to specifically target B lymphocytes in autoimmune conditions, such as T1D. RituxFab-Lipoplexes specifically bind to B lymphocytes of the human Raji cell line and of human PBMC of healthy donors. RituxFab-Lipoplexes have impact on the function of B lymphocytes of T1D patients upon CpG stimulation showing a higher inhibitory effect on total cell proliferation and IgM+ plasma cell differentiation than the not functionalized ones. These results might open new pathways of applicability of RituxFab-Lipoplexes, such as personalized immunotherapy, to other autoimmune disorders, where B lymphocytes are the prevalent pathogenic immunocytes.

M-CSF-Stimulated CD11b+ Myeloid Cells Induce Alopecia Areata in C3H/HeJ Mice

Alopecia areata (AA) is a T cell-mediated autoimmune skin disease with clinical features of hair loss and skin inflammation. It is unclear whether other immune cells except T lymphocytes are also involved in the development of AA. Here, our results reveal that dermal injection of either CD11b+ myeloid cells isolated from AA-affected skin or non-AA splenocyte-derived CD11b+ cells treated with macrophage colony-stimulating factor (M-CSF) induces AA in C3H/HeJ mice. The functional similarity of these cells in induction of AA seems to be due to a higher expression of M-CSF in AA affected skin. To explore the mechanism by which dermal injection of CD11b+ cells induce AA, we co-culture either AA derived skin cells or M-CSF-stimulated CD11b+ cells with naïve splenocytes. The results of splenocyte proliferation assay and immunoglobulin release in conditioned medium show a significant increase of splenocyte proliferation and IgG level in conditioned medium under both conditions as compared to controls. Most activated splenocytes induced by M-CSF-stimulated myeloid cells are B lymphocytes. B cell activation are further confirmed in AA-affected skin and skin draining lymph nodes of AA mice. In conclusion, in this study, we have provided evidence that M-CSF stimulated CD11b+ cells are able to induce AA in C3H/HeJ mice through a possible mechanism by activating B lymphocytes. This finding may provide insight for understanding the pathogenesis of AA.

Immune status of young pigs different methods of their breeding using means Globigen® Pig Doser and Globigen® Jump Start

The article deals with the influence of the use of means for young pigs Globigen® Pig Doser та Globigen® Jump Start, which due to the content of specific Ig Y have immunostimulatory properties. Assessing the level of nonspecific resistance of piglets, which are based on determining the content of T- and B-lymphocytes and their populations in the blood of animals 30-, 60- and 120-day-old, the trend of increasing the number of T-helpers, T-natural killers and B-lymphocytes in the experimental groups of animals of both farms. It was found that the content of T-helpers during single-phase rearing of pigs became more important under the action of Globigen® Pig Doser and ranged from 30.16−35.15 %, and during three-phase rearing – under the action of Globigen® Jump Start 34.58−35.08 %. An increase in the content of B-lymphocytes to the level of physiological norm was noted: FE PE “Glynjany Agro” (single-phase cultivation) in the first experimental group 16.75–19.45 %, in the second 17.66–21.11 %. At Ltd. “Meat Resources” (three-phase cultivation) 17.7–21.02 % and 18.91–21.01 %, respectively, in the first and second experimental groups. Regarding the indicators of the content of T-natural killers, there is a tendency to increase their number in the blood of animals of experimental groups by an average of 4.90 % for single-phase rearing and 3.09 % for three-phase rearing of pigs. Such data give grounds to claim that there is a formation of the immune response to the action of pathogens, which plays an important role in maintaining the barrier function of the intestinal mucosa, which in turn reduces mortality and increases the average daily gain of young pigs. Under the action of immunostimulants, the safety of piglets in FE PE “Glynjany Agro” (single-phase rearing) at 30 days of age increased to 81.3−93.7 %, and in Ltd. “Meat Resources” (three-phase rearing) to 80.0−86.7 %. In piglets FE PE “Glynjany Agro”, up to 120 days of age, the average daily gain was 0.710 and 0.691 kg using Globigen® Pig Doser and Globigen® Jump Start, and in piglets from Ltd. “Meat Resources” these figures were 0.595 and 0.628 kg.