BACKGROUND: HIV-exposed seronegative people who inject drugs (HESN-PWID) have been shown to have increased natural killer (NK) cell and myeloid activation when compared with control donors. METHODS: We investigated potential mechanisms maintaining NK activation by conducting quantitative proteome comparisons of NK cells from HESN-PWID subjects and control donors. Proteins upregulated in NK cells were measured in the plasma of HESN-PWID subjects by ELISA and further investigated for their ability to induce innate immune activation in vitro. RESULTS: The NK cell proteome comparison showed markedly higher levels of interferon-stimulated proteins and S100 proteins, including S100A14. Consistent with these results, we observed significantly higher levels of S100A14 in the plasma of HESN-PWID subjects compared with controls (P = 0.033, n = 25). In vitro, the addition of recombinant S100A14 protein significantly activated NK cells in a peripheral blood mononuclear cell mixture (P = 0.011, n = 9), but not purified NK cells alone. Treatment of purified monocytes with recombinant S100A14 protein induced secretion of TNF-alpha and led to significantly higher NK CD69 activation (P = 0.0156, n = 7) in a co-culture through a TLR4-dependent interaction. CONCLUSIONS: Our study identified S100A14 as a novel protein increased within NK cells and plasma of HESN-PWID subjects with the capacity to sustain NK activation through TLR4-dependent activation of myeloid cells.
BACKGROUND:HIV-exposed seronegative people who inject drugs (HESN-PWID) have been shown to have increased natural killer (NK) cell and myeloid activation when compared with control donors. METHODS: We investigated potential mechanisms maintaining NK activation by conducting quantitative proteome comparisons of NK cells from HESN-PWID subjects and control donors. Proteins upregulated in NK cells were measured in the plasma of HESN-PWID subjects by ELISA and further investigated for their ability to induce innate immune activation in vitro. RESULTS: The NK cell proteome comparison showed markedly higher levels of interferon-stimulated proteins and S100 proteins, including S100A14. Consistent with these results, we observed significantly higher levels of S100A14 in the plasma of HESN-PWID subjects compared with controls (P = 0.033, n = 25). In vitro, the addition of recombinant S100A14 protein significantly activated NK cells in a peripheral blood mononuclear cell mixture (P = 0.011, n = 9), but not purified NK cells alone. Treatment of purified monocytes with recombinant S100A14 protein induced secretion of TNF-alpha and led to significantly higher NK CD69 activation (P = 0.0156, n = 7) in a co-culture through a TLR4-dependent interaction. CONCLUSIONS: Our study identified S100A14 as a novel protein increased within NK cells and plasma of HESN-PWID subjects with the capacity to sustain NK activation through TLR4-dependent activation of myeloid cells.
Authors: M Biasin; S L Caputo; L Speciale; F Colombo; L Racioppi; A Zagliani; C Blé; F Vichi; L Cianferoni; A M Masci; M L Villa; P Ferrante; F Mazzotta; M Clerici Journal: J Infect Dis Date: 2000-10-09 Impact factor: 5.226
Authors: R Kaul; F A Plummer; J Kimani; T Dong; P Kiama; T Rostron; E Njagi; K S MacDonald; J J Bwayo; A J McMichael; S L Rowland-Jones Journal: J Immunol Date: 2000-02-01 Impact factor: 5.422
Authors: Hung K Tran; Loïc Chartier; Lien X Troung; Ngai N Nguyen; Arnaud Fontanet; François E Barré-Sinoussi; Gianfranco Pancino; Daniel Scott-Algara Journal: AIDS Res Hum Retroviruses Date: 2006-03 Impact factor: 2.205
Authors: A Verani; G Scarlatti; M Comar; E Tresoldi; S Polo; M Giacca; P Lusso; A G Siccardi; D Vercelli Journal: J Exp Med Date: 1997-03-03 Impact factor: 14.307