16 research outputs found

    Brugia malayi Antigen (BmA) inhibits HIV-1 trans-infection but neither BmA nor ES-62 alter HIV-1 infectivity of DC induced CD4+ Th-cells

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    One of the hallmarks of HIV-1 disease is the association of heightened CD4+ T-cell activation with HIV-1 replication. Parasitic helminths including filarial nematodes have evolved numerous and complex mechanisms to skew, dampen and evade human immune responses suggesting that HIV-1 infection may be modulated in co-infected individuals. Here we studied the effects of two filarial nematode products, adult worm antigen from Brugia malayi (BmA) and excretory-secretory product 62 (ES-62) from Acanthocheilonema viteae on HIV-1 infection in vitro. Neither BmA nor ES-62 influenced HIV-1 replication in CD4+ enriched T-cells, with either a CCR5- or CXCR4-using virus. BmA, but not ES-62, had the capacity to bind the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) thereby inhibiting HIV-1 trans-infection of CD4+ enriched T-cells. As for their effect on DCs, neither BmA nor ES-62 could enhance or inhibit DC maturation as determined by CD83, CD86 and HLA-DR expression, or the production of IL-6, IL-10, IL-12 and TNF-α. As expected, due to the unaltered DC phenotype, no differences were found in CD4+ T helper (Th) cell phenotypes induced by DCs treated with either BmA or ES-62. Moreover, the HIV-1 susceptibility of the Th-cell populations induced by BmA or ES-62 exposed DCs was unaffected for both CCR5- and CXCR4-using HIV-1 viruses. In conclusion, although BmA has the potential capacity to interfere with HIV-1 transmission or initial viral dissemination through preventing the virus from interacting with DCs, no differences in the Th-cell polarizing capacity of DCs exposed to BmA or ES-62 were observed. Neither antigenic source demonstrated beneficial or detrimental effects on the HIV-1 susceptibility of CD4+ Th-cells induced by exposed DCs

    Acute Muscular Sarcocystosis: An International Investigation Among Ill Travelers Returning From Tioman Island, Malaysia, 2011-2012

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    A large outbreak of acute muscular sarcocystosis (AMS) among international tourists who visited Tioman Island, Malaysia, is described. Clinicians evaluating travelers returning ill from Malaysia with myalgia, with or without fever, should consider AMS in their differential diagnosi

    Diagnostic performance of sacroiliac joint MRI and added value of spine MRI to detect active spondyloarthritis.

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    To investigate the diagnostic performance of sacroiliac joint (SIJ) magnetic resonance imaging (MRI) and the incremental value of spine MRI to "predict" clinical disease activity in patients with axial spondyloarthritis (axSpA). This cross-sectional study included adult patients with known axSpA according to the SpondyloArthritis International Society (ASAS) classification criteria, radiological arm. MRI disease activity was scored semi-quantitatively for SIJ and total spine MRI in each patient. Two cut-off levels (≄ 1.3 and ≄ 2.1) for ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP) were considered for clinical disease activity categorization. MRI scores were first evaluated individually. Then, SIJ score was combined with the score from a spine segment (lumbar, cervical, thoracic or total spine) to build a bi-parametric model using a classification tree. Receiver operating characteristic (ROC) curves were constructed to evaluate the classification performance according to disease activity category of these models. Forty-four patients (30 men, 14 women; mean age, 37 years±10 [SD] [range: 17-64 years]) with a mean disease duration of 5 years±8 (SD) (range: 0-35 years) were included. Thirty-six patients (36/44; 82%) had ASDAS-CRP≄1.3 and 27 patients (27/44; 61%) had ASDAS-CRP≄2.1. The most frequently involved spinal segment was mid-thoracic (T7-T8). The SIJ MRI score was an informative model to identify active axSpA (AUC≄0.7, regardless of the cut-off level on ASDAS-CRP). Performance of bi-parametric models based on "SIJ+thoracic spine" (for detecting patients with ASDAS-CRP≄1.3) or "SIJ+total spine" (for detecting patients with ASDAS-CRP≄2.1) outperformed that of the individual SIJ score (P<0.05). The combination of MRI of the SIJ and spine allows to accurately discriminate between active and inactive axSpA, outperforming SIJ MRI alone

    Interleukin‐12 modulates T‐cell responses to microfilariae but fails to abrogate interleukin‐5‐dependent immunity in a mouse model of onchocerciasis

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    Infection of mice with microfilariae of Onchocerca lienalis induces high levels of protective immunity to reinfection, which is dependent on interleukin (IL)‐5 but not IL‐4. Here, we have investigated the effect of exogenous IL‐12 administration during either the priming or effector phases of the immune response. When administered during priming, IL‐12 induced down‐regulation of parasite‐specific serum immunoglobulin (Ig)E and up‐regulation of IgG2a. Antigen‐specific IL‐4 responses were strongly suppressed, whilst blood eosinophil levels were partially reduced. When administered during a challenge infection, IL‐12 did not significantly influence the balance of antibody isotypes, but partially reduced eosinophil production. Antigen‐specific IL‐4 responses were again completely ablated. Unusually, interferon‐γ (IFN‐γ) responses were not significantly affected following IL‐12 administration, either during priming or after challenge infections. Moreover, despite a fall in antigen‐specific IL‐5 production, the expression of IL‐5‐dependent immunity, as determined by reduction in worm recoveries, was fully maintained. These data demonstrate that parasite‐induced IL‐4 can be abrogated without affecting protective immunity to Onchocerca microfilariae in mice. In view of the established role of IL‐4 in pathogenesis, this may have important implications for the development of immunoprophylaxis aimed at microfilariae and the alleviation of pathology in onchocerciasis
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