scholarly journals Differential Gene Expression Analysis of Placentas with Increased Vascular Resistance and Pre-Eclampsia Using Whole-Genome Microarrays

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
M. Centlow ◽  
C. Wingren ◽  
C. Borrebaeck ◽  
M. J. Brownstein ◽  
S. R. Hansson

Pre-eclampsia is a pregnancy complication characterized by hypertension and proteinuria. There are several factors associated with an increased risk of developing pre-eclampsia, one of which is increased uterine artery resistance, referred to as “notching”. However, some women do not progress into pre-eclampsia whereas others may have a higher risk of doing so. The placenta, central in pre-eclampsia pathology, may express genes associated with either protection or progression into pre-eclampsia. In order to search for genes associated with protection or progression, whole-genome profiling was performed. Placental tissue from 15 controls, 10 pre-eclamptic, 5 pre-eclampsia with notching, and 5 with notching only were analyzed using microarray and antibody microarrays to study some of the same gene product and functionally related ones. The microarray showed 148 genes to be significantly altered between the four groups. In the preeclamptic group compared to notch only, there was increased expression of genes related to chemotaxis and the NF-kappa B pathway and decreased expression of genes related to antigen processing and presentation, such as human leukocyte antigen B. Our results indicate that progression of pre-eclampsia from notching may involve the development of inflammation. Increased expression of antigen-presenting genes, as seen in the notch-only placenta, may prevent this inflammatory response and, thereby, protect the patient from developing pre-eclampsia.

2020 ◽  
Vol 177 (2) ◽  
pp. 454-465 ◽  
Author(s):  
James C Waddington ◽  
Xiaoli Meng ◽  
Patricia T Illing ◽  
Arun Tailor ◽  
Kareena Adair ◽  
...  

Abstract Flucloxacillin is a β-lactam antibiotic associated with a high incidence of drug-induced liver reactions. Although expression of human leukocyte antigen (HLA)-B*57:01 increases susceptibility, little is known of the pathological mechanisms involved in the induction of the clinical phenotype. Irreversible protein modification is suspected to drive the reaction through the modification of peptides that are presented by the risk allele. In this study, the binding of flucloxacillin to immune cells was characterized and the nature of the peptides presented by HLA-B*57:01 was analyzed using mass spectrometric-based immunopeptidomics methods. Flucloxacillin modification of multiple proteins was observed, providing a potential source of neoantigens for HLA presentation. Of the peptides eluted from flucloxacillin-treated C1R-B*57:01 cells, 6 putative peptides were annotated as flucloxacillin-modified HLA-B*57:01 peptide ligands (data are available via ProteomeXchange with identifier PXD020137). To conclude, we have characterized naturally processed drug-haptenated HLA ligands presented on the surface of antigen presenting cells that may drive drug-specific CD8+ T-cell responses.


Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 527
Author(s):  
Paula Constanza Arriola Benitez ◽  
Ayelén Ivana Pesce Viglietti ◽  
María Mercedes Elizalde ◽  
Guillermo Hernán Giambartolomei ◽  
Jorge Fabián Quarleri ◽  
...  

In Brucellosis, the role of hepatic stellate cells (HSCs) in the induction of liver fibrosis has been elucidated recently. Here, we study how the infection modulates the antigen-presenting capacity of LX-2 cells. Brucella abortus infection induces the upregulation of class II transactivator protein (CIITA) with concomitant MHC-I and -II expression in LX-2 cells in a manner that is independent from the expression of the type 4 secretion system (T4SS). In concordance, B. abortus infection increases the phagocytic ability of LX-2 cells and induces MHC-II-restricted antigen processing and presentation. In view of the ability of B. abortus-infected LX-2 cells to produce monocyte-attracting factors, we tested the capacity of culture supernatants from B. abortus-infected monocytes on MHC-I and –II expression in LX-2 cells. Culture supernatants from B. abortus-infected monocytes do not induce MHC-I and -II expression. However, these supernatants inhibit MHC-II expression induced by IFN-γ in an IL-10 dependent mechanism. Since hepatocytes constitute the most abundant epithelial cell in the liver, experiments were conducted to determine the contribution of these cells in antigen presentation in the context of B. abortus infection. Our results indicated that B. abortus-infected hepatocytes have an increased MHC-I expression, but MHC-II levels remain at basal levels. Overall, B. abortus infection induces MHC-I and -II expression in LX-2 cells, increasing the antigen presentation. Nevertheless, this response could be modulated by resident or infiltrating monocytes/macrophages.


2020 ◽  
Vol 21 (3) ◽  
pp. 687
Author(s):  
Marlene Bravo-Parra ◽  
Marina Arenas-Padilla ◽  
Valeria Bárcenas-Preciado ◽  
Jesús Hernández ◽  
Verónica Mata-Haro

MicroRNAs (miRNAs) mediate the regulation of gene expression. Several reports indicate that probiotics induce miRNA-mediated immunomodulation at different levels, such as cytokine production and the up-regulation of several markers related to antigen presentation in antigen-presenting cells. The objective of this work was to identify target genes of miRNAs that are involved in the processing and presentation of antigens in monocyte-derived dendritic cells (moDCs) stimulated with the probiotic Bifidobacterium animalis ssp. lactis BB12 (BB12). First, an in silico prediction analysis for a putative miRNA binding site within a given mRNA target was performed using RNAHybrid software with mature sequences of differentially expressed miRNAs retrieved from a Genbank data set that included BB12-stimulated and unstimulated porcine monocytes. From them, 23 genes resulted in targets of 19 miRNAs, highlighting miR-30b-3p, miR-671-5p, and miR-9858-5p, whose targets were costimulatory molecules, and were overexpressed (p < 0.05) in BB12-stimulated moDCs. The analysis of moDCs showed that the percentage of cells expressing SLA-DR+CD80+ decreased significantly (p = 0.0081) in BB12-stimulated moDCs; interleukin (IL)-10 production was unchanged at 6 h but increased after 24 h of culture in the presence of BB12 (p < 0.001). In summary, our results suggest that SLA-DR and CD80 can be down-regulated by miRNAs miR-30b-3p, miR-671-5p, and miR-9858-5p, while miR-671-5p targets IL-10.


Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2865-2871 ◽  
Author(s):  
GC Manara ◽  
P Sansoni ◽  
L Badiali-De Giorgi ◽  
G Gallinella ◽  
C Ferrari ◽  
...  

Abstract A possible role of the peptide binding protein (PBP) 72/74 in antigen processing and presentation has been recently suggested in mice. In order to evaluate a possible analogous role of a PBP72/74-related protein in humans, immunoelectron microscope investigations, functional studies, and immunofluorescence analyses were performed on normal human peripheral antigen-presenting cells. We demonstrated that the determinant recognized by antiheat shock protein (HSP) 72/73 monoclonal antibody (MoAb) is constitutively expressed on the cell surface of monocytes as well as of B cells. Moreover, the capability of monocytes to present a recall antigen to T cells was significantly decreased when preincubated with an anti-HSP72/73 MoAb. These data add further strength to a potential role of a protein related to human PBP72/74 homologue in antigen processing and/or presentation. Finally, the capability of anti-HSP72/73 MoAb to impair the ability of fixed monocytes to present a synthetic peptide demonstrates that cell surface- localized PBP72/74-related protein could play a role in antigen presentation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hendrik J. P. van der Zande ◽  
Dominik Nitsche ◽  
Laura Schlautmann ◽  
Bruno Guigas ◽  
Sven Burgdorf

The mannose receptor is a member of the C-type lectin (CLEC) family, which can bind and internalize a variety of endogenous and pathogen-associated ligands. Because of these properties, its role in endocytosis as well as antigen processing and presentation has been studied intensively. Recently, it became clear that the mannose receptor can directly influence the activation of various immune cells. Cell-bound mannose receptor expressed by antigen-presenting cells was indeed shown to drive activated T cells towards a tolerogenic phenotype. On the other hand, serum concentrations of a soluble form of the mannose receptor have been reported to be increased in patients suffering from a variety of inflammatory diseases and to correlate with severity of disease. Interestingly, we recently demonstrated that the soluble mannose receptor directly promotes macrophage proinflammatory activation and trigger metaflammation. In this review, we highlight the role of the mannose receptor and other CLECs in regulating the activation of immune cells and in shaping inflammatory responses.


1991 ◽  
Vol 1 (3) ◽  
pp. 137-148 ◽  
Author(s):  
Abbe N. Vallejo ◽  
Norman W. Miller ◽  
L. William Clem

This work was undertaken to investigate whether or not antigen processing and presentation are important in channel catfish in vitro secondary immune responses elicited with structurally defined proteins, namely, pigeon heart cytochrome C (pCytC), hen egg lysozyme, and horse myoglobin. The use ofin vitroantigen-pulsed and fixed B cells or monocytes as antigen presenting cells (APC) resulted in autologous peripheral blood leukocytes (PBL) responding with vigorous proliferation and antibody productionin vitro. In addition, several long-term catfish monocyte lines have been found to function as efficient APC with autologous but not allogeneic responders. Subsequent separation of the responding PBL into sIg-(T-cell-enriched) and B (sIg+) cell subsets showed that both underwent proliferative responses to antigen-pulsed and fixed APC. Moreover, allogeneic cells used as APC were found to induce only strong mixed leukocyte reactions without specificin vitroantibody production. Initial attempts at identifying the immunogenic region(s) of the protein antigens for catfish indicated there are two such regions for pCytC, namely, peptides 66-80 and 81-104.


Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2865-2871
Author(s):  
GC Manara ◽  
P Sansoni ◽  
L Badiali-De Giorgi ◽  
G Gallinella ◽  
C Ferrari ◽  
...  

A possible role of the peptide binding protein (PBP) 72/74 in antigen processing and presentation has been recently suggested in mice. In order to evaluate a possible analogous role of a PBP72/74-related protein in humans, immunoelectron microscope investigations, functional studies, and immunofluorescence analyses were performed on normal human peripheral antigen-presenting cells. We demonstrated that the determinant recognized by antiheat shock protein (HSP) 72/73 monoclonal antibody (MoAb) is constitutively expressed on the cell surface of monocytes as well as of B cells. Moreover, the capability of monocytes to present a recall antigen to T cells was significantly decreased when preincubated with an anti-HSP72/73 MoAb. These data add further strength to a potential role of a protein related to human PBP72/74 homologue in antigen processing and/or presentation. Finally, the capability of anti-HSP72/73 MoAb to impair the ability of fixed monocytes to present a synthetic peptide demonstrates that cell surface- localized PBP72/74-related protein could play a role in antigen presentation.


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