scholarly journals Phagocytosis of the Malarial Pigment, Hemozoin, Impairs Expression of Major Histocompatibility Complex Class II Antigen, CD54, and CD11c in Human Monocytes

1998 ◽  
Vol 66 (4) ◽  
pp. 1601-1606 ◽  
Author(s):  
Evelin Schwarzer ◽  
Massimo Alessio ◽  
Daniela Ulliers ◽  
Paolo Arese
Keyword(s):  
Immune Response ◽  
Protein Kinase C ◽  
Major Histocompatibility Complex ◽  
Protein Kinase ◽  
Class Ii ◽  
Fc Receptor ◽  
Human Monocytes ◽  
Major Histocompatibility ◽  
Kinase C ◽  
Histocompatibility Complex

ABSTRACT In Plasmodium falciparum malaria, large proportions of resident macrophages and circulating monocytes and leukocytes contain massive amounts of the malarial pigment, hemozoin. Previous studies have shown that important functions (e.g., the generation of the oxidative burst, the ability to repeat phagocytosis, and protein kinase C activity) were severely impaired in hemozoin-loaded monocytes. Expression of membrane antigens directly involved in the immune response and in the phagocytic process, and/or under protein kinase C control, in hemozoin-loaded human monocytes was studied. Expression of major histocompatibility complex (MHC) class II after gamma interferon stimulation was blocked in hemozoin-loaded monocytes at the protein expression and gene transcription levels but was preserved in control monocytes loaded with opsonized latex beads or anti-D(Rho)-immunoglobulin G (IgG)-opsonized human erythrocytes. Expression of CD54 (intracellular adhesion molecule 1) and CD11c (p150,95 integrin) was also decreased in hemozoin-loaded monocytes. Expression of MHC class I, CD16 (low-affinity Fc receptor for aggregated IgG), CD32 (low-affinity Fc receptor for aggregated IgG), CD64 (high-affinity receptor for IgG), CD11b (receptor for complement component iC3b [CR3]), CD35 (receptor for complement components C3b and C4b [CR1]), and CD36 (non-class-A scavenger receptor) was not specifically affected by hemozoin loading. These results suggest that hemozoin loading may contribute to the impairment of the immune response and the derangement of antigen presentation reported in previous studies of P. falciparum malaria.

scholarly journals Downregulation of CIITA Function by Protein Kinase A (PKA)-Mediated Phosphorylation: Mechanism of Prostaglandin E, Cyclic AMP, and PKA Inhibition of Class II Major Histocompatibility Complex Expression in Monocytic Lines

2001 ◽  
Vol 21 (14) ◽  
pp. 4626-4635 ◽  
Author(s):  
Guoxuan Li ◽  
Jonathan A. Harton ◽  
Xinsheng Zhu ◽  
Jenny P.-Y. Ting
Keyword(s):  
Major Histocompatibility Complex ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Class Ii ◽  
Prostaglandin E ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Class Ii Mhc ◽  
Kinase A

ABSTRACT Prostaglandins, pleiotropic immune modulators that induce protein kinase A (PKA), inhibit gamma interferon induction of class II major histocompatibility complex (MHC) genes. We show that phosphorylation of CIITA by PKA accounts for this inhibition. Treatment with prostaglandin E or 8-bromo-cyclic AMP or transfection with PKA inhibits the activity of CIITA in both mouse and human monocytic cell lines. This inhibition is independent of other transcription factors for the class II MHC promoter. These same treatments also greatly reduced the induction of class II MHC mRNA by CIITA. PKA phosphorylation sites were identified using site-directed mutagenesis and phosphoamino acid analysis. Phosphorylation at CIITA serines 834 and 1050 accounts for the inhibitory effects of PKA on CIITA-driven class II MHC transcription. This is the first demonstration that the posttranslational modification of CIITA mediates inhibition of class II MHC transcription.

scholarly journals Engagement of major histocompatibility complex class II molecules induces sustained, lymphocyte function-associated molecule 1-dependent cell adhesion.

1990 ◽  
Vol 172 (5) ◽  
pp. 1513-1516 ◽  
Author(s):  
W Mourad ◽  
R S Geha ◽  
T Chatila
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Protein Kinase ◽  
Major Histocompatibility Complex Class ◽  
Qualitative Change ◽  
Class Ii ◽  
Lymphocyte Function ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

Antigenic stimulation is associated with enhanced adhesion between T cells and antigen-presenting cells (APC). Binding of ligands to the T cell antigen receptor activates the adhesion function of lymphocyte function-associated molecule 1 (LFA-1; CD11a/CD18). We demonstrate here that ligand binding to major histocompatibility complex class II (Ia) molecules also activates LFA-1 function, providing a reciprocal mechanism for the induction of adhesion between T cells and Ia+ APC. Adhesion was affected by a qualitative change in LFA-1 molecules and was reversed by the protein kinase C inhibitor sphingosine. These results define a novel role for Ia molecules as signal transducing receptors that regulate LFA-1-dependent adhesion via a putative, Ia-coupled protein kinase(s).

scholarly journals Postoperative abdominal sepsis induces selective and persistent changes in CTCF binding within the MHC-II region of human monocytes

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0250818
Author(s):  
Benedikt Hermann Siegler ◽  
Marc Altvater ◽  
Jan Niklas Thon ◽  
Christopher Neuhaus ◽  
Christoph Arens ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Transcriptional Response ◽  
Class Ii ◽  
Ctcf Binding ◽  
Human Monocytes ◽  
Complex Class ◽  
Postoperative Sepsis ◽  
Major Histocompatibility ◽  
Mhc Ii ◽  
Histocompatibility Complex

Background Postoperative abdominal infections belong to the most common triggers of sepsis and septic shock in intensive care units worldwide. While monocytes play a central role in mediating the initial host response to infections, sepsis-induced immune dysregulation is characterized by a defective antigen presentation to T-cells via loss of Major Histocompatibility Complex Class II DR (HLA-DR) surface expression. Here, we hypothesized a sepsis-induced differential occupancy of the CCCTC-Binding Factor (CTCF), an architectural protein and superordinate regulator of transcription, inside the Major Histocompatibility Complex Class II (MHC-II) region in patients with postoperative sepsis, contributing to an altered monocytic transcriptional response during critical illness. Results Compared to a matched surgical control cohort, postoperative sepsis was associated with selective and enduring increase in CTCF binding within the MHC-II. In detail, increased CTCF binding was detected at four sites adjacent to classical HLA class II genes coding for proteins expressed on monocyte surface. Gene expression analysis revealed a sepsis-associated decreased transcription of (i) the classical HLA genes HLA-DRA, HLA-DRB1, HLA-DPA1 and HLA-DPB1 and (ii) the gene of the MHC-II master regulator, CIITA (Class II Major Histocompatibility Complex Transactivator). Increased CTCF binding persisted in all sepsis patients, while transcriptional recovery CIITA was exclusively found in long-term survivors. Conclusion Our experiments demonstrate differential and persisting alterations of CTCF occupancy within the MHC-II, accompanied by selective changes in the expression of spatially related HLA class II genes, indicating an important role of CTCF in modulating the transcriptional response of immunocompromised human monocytes during critical illness.

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