DEAD-box proteins, like Leishmania eIF4A, modulate interleukin (IL)-12, IL-10 and tumour necrosis factor-alpha production by human monocytes.
Previously we showed that His-tagged, recombinant, Leishmania infantum eukaryotic initiation factor (LeIF) was both an RNA-dependent ATPase and an ATP-dependent RNA helicase in vitro, as described for other members of the DEAD-box helicase family. In addition, we showed that LeIF induces the production of IL-12, IL-10, and TNF-α by human monocytes. This study aims to characterize the cytokine-inducing activity in human monocytes of several proteins belonging to the DEAD-box family from mammals and yeast. All tested proteins contained the 11 conserved motifs (Q, I, Ia, GG Ib, II, III, IV, QxxR, V and VI) characteristic of DEAD-box proteins, but they have different biological functions and different percentages of identities with LeIF. We show that these mammalian or yeast recombinant proteins also are able to induce IL-12, IL-10 and TNF-α secretion by monocytes of healthy human subjects. This cytokine-inducing activity is proteinase K sensitive and polymyxin B resistant. Our results show that the induction of cytokines in human monocytes is not unique to the protein LeIF of Leishmania, and it suggests that the activity of certain DEAD-box proteins can be exploited as adjuvant and/or to direct immune responses towards a Th1 profile in vaccination or immunotherapy protocols.
Laboratoire d'Epidémiologie et d'Ecologie Parasitaire/Laboratoire d'Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée (LR11IPT04), Institut Pasteur de Tunis-Université Tunis El Manar, Tunis-Belvédère, Tunisia.
M
M
Barhoumi
A
A
Meddeb-Garnaoui
N K
NK
Tanner
J
J
Banroques
B
B
Kaabi
I
I
Guizani
D000276:Adjuvants, Immunologic; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D039601:Eukaryotic Initiation Factor-4A / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D018314:Leishmania infantum / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D029701:Saccharomyces cerevisiae Proteins / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000276:Adjuvants, Immunologic; C109242:FAL1 protein, S cerevisiae; C092810:LeIF protein, Leishmania; D010448:Peptide Initiation Factors; D015800:Protozoan Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D039601:Eukaryotic Initiation Factor-4A; C492152:DED1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases