Accession Number : ADA536161


Title :   Activation of MyD88 Signaling upon Staphylococcal Enterotoxin Binding to MHC Class II Molecules


Descriptive Note : Journal article


Corporate Author : ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD


Personal Author(s) : Kissner, Teri L ; Ruthel, Gordon ; Alam, Shahabuddin ; Ulrich, Robert G ; Fernandez, Stefan ; Saikh, Kamal U


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a536161.pdf


Report Date : 20 Jan 2011


Pagination or Media Count : 14


Abstract : Ligands binding to Toll-like receptor (TLR), interleukin 1 receptor (IL-1R), or IFN-cR1 are known to trigger MyD88-mediated signaling, which activates pro-inflammatory cytokine responses. Recently we reported that staphylococcal enterotoxins (SEA or SEB), which bind to MHC class II molecules on APCs and cross link T cell receptors, activate MyD88-mediated proinflammatory cytokine responses. We also reported that MyD882/2 mice were resistant to SE- induced toxic shock and had reduced levels of serum cytokines. In this study, we investigated whether MHC class II- SE interaction by itself is sufficient to activate MyD88 in MHC class II+ cells and induce downstream pro-inflammatory signaling and production of cytokines such as TNF-a and IL-1b. Here we report that human monocytes treated with SEA, SEB, or anti-MHC class II monoclonal antibodies up regulated MyD88 expression, induced activation of NF-kB, and increased expression of IL-1R1 accessory protein, TNF-a and IL-1b. MyD88 immunoprecipitated from cell extracts after SEB stimulation showed a greater proportion of MyD88 phosphorylation compared to unstimulated cells indicating that MyD88 was a component of intracellular signaling. MyD88 downstream proteins such as IRAK4 and TRAF6 were also up regulated in monocytes after SEB stimulation. In addition to monocytes, primary B cells up regulated MyD88 in response to SEA or SEB stimulation. Importantly, in contrast to primary B cells, MHC class II deficient T2 cells had no change of MyD88 after SEA or SEB stimulation, whereas MHC class II-independent activation of MyD88 was elicited by CpG or LPS. Collectively, these results demonstrate that MHC class II utilizes a MyD88-mediated signaling mechanism when in contact with ligands such as SEs to induce pro-inflammatory cytokines.


Descriptors :   *B LYMPHOCYTES , *PROTEINS , *STAPHYLOCOCCUS , LIGANDS , MICE , T LYMPHOCYTES , MONOCYTES , CELLS(BIOLOGY) , INFLAMMATION , RIBONUCLEIC ACIDS , RECEPTOR SITES(PHYSIOLOGY) , PHOSPHORYLATION , CHEMILUMINESCENCE , PHOSPHORUS TRANSFERASES , GRAPHS , CYTOKINES , REPRINTS , MOLECULES


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE