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2.
Oncotarget ; 7(46): 74592-74601, 2016 11 15.
Article in English | MEDLINE | ID: mdl-27780938

ABSTRACT

Sézary syndrome (SS) carries a poor prognosis, and infections represent the most frequent cause of death in SS patients. Toll-like receptors (TLRs) are a family of innate immune receptors that induce protective immune responses against infections. We sought to evaluate the ability of TLR agonists to induce inflammatory cytokine, Th2 cytokine, and type I interferon (IFN-I) production by peripheral blood mononuclear cells (PBMC) of untreated SS patients. We detected impaired IL-6, IL-10 and IL-13 secretion by PBMC induced by the agonists for TLR5, TLR3, TLR7 and TLR9 in SS patients, while it was partially recovered by TLR2/TLR4 and TLR7/8 agonists TNF secretion was restored following stimulation with TLR2/TLR4 agonists. IFN-γ was scarcely produced upon TLR activation in SS cells, albeit TLR 7/8 (CL097) enhanced their secretion at lower levels than the control group. TLR9 agonist efficiently induced IFN-I in SS patients, although this positive regulation was not observed for other cytokines, in direct contrast to the broad activity of CL097. Among the TLR agonists, TLR4 was able to induce pro-inflammatory, IL-10 and Th2 secretion, while TLR7-8 agonist induced the inflammatory cytokines, IFN-I and IFN-γ. These findings reveal a dysfunctional cytokine response upon both extracellular and intracellular TLR activation in SS patients, which was partially restored by TLRs agonists.


Subject(s)
Cytokines/metabolism , Inflammation Mediators/metabolism , Interferon Type I/metabolism , Sezary Syndrome/metabolism , Toll-Like Receptors/agonists , Aged , Cytokines/blood , Female , Humans , Immunity, Innate , Inflammation Mediators/blood , Interferon Type I/blood , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Sezary Syndrome/blood , Sezary Syndrome/immunology
3.
Sci Rep ; 6: 25875, 2016 05 11.
Article in English | MEDLINE | ID: mdl-27168019

ABSTRACT

Individuals who remain HIV-seronegative despite repeated unprotected exposure to the virus are defined as exposed seronegative (ESN) individuals. Innate and adaptive immunity, as well as genetic factors, provide ESNs with important advantages that allow for low infection susceptibility. The majority of HIV-1-infected individuals undergo antiretroviral therapy, which can decrease the level of HIV-1 exposure in ESNs. We analyzed type I interferon (IFN)-related antiviral and regulatory factors in peripheral blood mononuclear cells (PBMCs) and oral epithelial cells from serodiscordant couples. Our findings revealed that ESNs did not induce the expression of antiviral factors (APOBEC-3G, TRIM5-α, SAMDH1, STING, TBk1) or regulatory factors (Trex, Foxo3, Socs3, IL-10) in PBMCs, unlike their HIV-1-infected partners. In contrast, ESNs upregulated APOBEC-3G and type I/III IFNs (IFNs-α,-ß/-λ) in oral mucosal epithelial cells similar to their HIV-infected partners. The serodiscordant groups exhibited an increased expression of type I IFN-induced regulators, such as Trex and Foxo3, in oral epithelial cells. TLR7, TLR8 and TLR9 were expressed in oral epithelial cells of both ESNs and HIV-1-infected subjects. These findings revealed evidence of antiviral factors, type I/III interferon and regulatory factor expression only in the oral mucosal compartment of ESNs, while HIV-1-infected partners systemically and oral mucosal expressed the antiviral profile.


Subject(s)
Antiviral Agents/metabolism , HIV Infections/drug therapy , Interferon-alpha/metabolism , Interferon-beta/metabolism , Interferon-gamma/metabolism , Mouth/immunology , Adaptive Immunity , Adult , Epithelial Cells/cytology , Epithelial Cells/immunology , Epithelial Cells/metabolism , Epithelial Cells/virology , Female , HIV Infections/immunology , HIV Infections/metabolism , HIV Seronegativity , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/virology , Male , Middle Aged , Mouth/cytology , Mouth/metabolism , Mouth/virology , Sexual Partners
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