S100A9 tetramers, which are ligands of CD85j, increase the ability of MVAHIV-primed NK cells to control HIV infection

Abstract

Natural killer (NK) cells are the major antiviral effector population of the innate immune system. We previously found that S100A9 is a novel ligand of the receptor CD85j and that S100A9 tetramers enhance the anti-HIV activity of NK cells. Also, we found that dendritic cells (DCs) infected by the HIV vaccine candidate, MVAHIV, prime NK cells to specifically control HIV infection in autologous CD4+ T cells. In this study, we analyzed whether stimulation of NK cells by S100A9 tetramers prior to the priming by MVAHIV-infected DCs modulates the subsequent anti-HIV activity of NK cells. We found that S100A9 tetramers activate NK cells and that DCs enhance the anti-HIV activity of NK cells. Interestingly, we observed that stimulation of NK cells by S100A9 tetramers, prior to the priming, significantly increased the subsequent anti-HIV activity of NK cells and that the enhanced anti-HIV activity was observed following different conditions of priming, including the MVAHIV-priming. As S100A9 tetramers alone directly increase the anti-HIV activity of NK cells and as this increased anti-HIV activity is also observed following the interaction of NK cells with MVAHIV-infected DCs, we propose S100A9 tetramers as potential adjuvants to stimulate the anti-HIV activity of NK cells.

Pathological roles of MRP14 in anemia and splenomegaly during experimental visceral leishmaniasis

“…But, the major source of IFN-γ during L. donovani infection may not be T cells since antigen-specific induction of IFN-γ production was not observed in splenocytes from the infected MRP14KO mice (Fig 4) NK cells and ILC1 cells are known innate immune cells as a source of IFN-γ [50]. MRP14 can activate NK cells and support IFN-γ production [51,52], suggesting the molecule affects immune responses through direct activation of innate immunity rather than manipulating acquired immunity.…”

Autoimmune arthritis induces paired immunoglobulin‐like receptor B expression on CD4+ T cells from SKG mice

“…Such an inhibitory function of PIR‐B in chronic arthritis could subsequently be even more effective at sites of chronic inflammation. PIR‐B has been reported to bind S100 A9 (also known as migration inhibitory factor‐related protein 14 ‐MRP14‐ or calgranulin B) , which is overexpressed in rheumatoid synovium and is found in increased concentration both in serum and synovial fluid of patients with RA , while a decrease in S100A9 serum concentrations is associated with clinical improvement of the symptoms . In addition, the human nonclassical MHC molecule HLA‐G is also a ligand for LIR‐1 and PIR‐B and treatment with soluble HLA‐G produces excellent antiinflammatory effects in collagen‐induced arthritis .…”

Alarming and Calming: Opposing Roles of S100A8/S100A9 Dimers and Tetramers on Monocytes

“…[ 6 , 7 , 14 , 28 ] Moreover, S100A8/S100A9 complexes have been described to bind to several other receptors, for example, TLR4, RAGE, CD33, CD68, CD69, CD85j, EMMPRIN (CD147), or MCAM, but none of these published interactions could explain a specific effect of the S100A8/S100A9‐tetramers. [ 25 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] In the presence of high extracellular calcium‐ion concentrations alone or in combination with zinc‐, nickel‐, or manganese‐ions, the S100A8/S100A9‐dimers form S100A8/S100A9‐tetramers, which mask the TLR4 binding site in the tetramer interface and block binding to TLR4. [ 8 , 15 , 16 ] The tetramers diffuse into the systemic circulation, where they can be found in relatively high concentrations.…”