Patricia Byrne

Publications (3)13.27 Total impact

• Article: A novel phospholipid-based drug formulation, VP025, modulates age- and LPS-induced microglial activity in the rat.

  Darren S D Martin, Michelle Walsh, Anne-Marie Miller, Helen E Skerrett, Patricia Byrne, Arkady Mandel, Anthony E Bolton, Marina A Lynch
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  ABSTRACT: A common change that occurs with age in the central nervous system is an increase in microglial-associated inflammation. This is usually coupled with an increase in the concentration of the inflammatory cytokine interleukin-1beta (IL-1beta) in the hippocampus and an inhibition in long-term potentiation. To assess the effects of a novel preparation of phospholipid nanoparticles incorporating phosphatidylglycerol, VP025, on inflammatory changes in hippocampus of aged and lipopolysaccharide (LPS)-treated rats. We report that a possible initial target cell of the putative anti-inflammatory actions of VP025 may be macrophages, as VP025 is engulfed by, and has the capacity to alter the activity of, these cells. VP025 reversed the increase in IFN-gamma concentration in supernatant taken from peritoneal macrophages harvested from LPS-treated rats. In addition, markers of microglial activity, major histocompatibility complex class II (MHC II) mRNA expression, CD40 expression and IL-1beta concentration were increased, and CD200 expression was reduced, in the hippocampus of these rats. VP025 reversed changes in CD40, IL-1beta and CD200 in aged rats, and also restored long-term potentiation in aged and LPS-treated rats. We conclude that VP025 has the ability to modulate the activity of macrophage, microglia and neurons in response to stressors such as ageing and LPS treatment.
  NeuroImmunoModulation 08/2009; 16(6):400-10. · 2.38 Impact Factor
• Article: Depletion of NK cells results in disseminating lethal infection with Bordetella pertussis associated with a reduction of antigen-specific Th1 and enhancement of Th2, but not Tr1 cells.

  Patricia Byrne, Peter McGuirk, Stephen Todryk, Kingston H G Mills
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  ABSTRACT: IFN-gamma plays a critical role in protection against Bordetella pertussis, but Th1 cells are only detectable after the infection has started to resolve, suggesting a protective role for innate IFN-gamma early in infection. Here, we demonstrate significant recruitment of NK cells and NKT cells into the lungs following respiratory challenge with B. pertussis. Furthermore, NK cells are the primary source of IFN-gamma in the lungs during the acute stage of infection. Stimulation of IFN-gamma production by NK cells was indirect through B. pertussis-activated IL-12 or IL-23 production by dendritic cells. Depletion of NK cells with anti-asialo ganglio-N-tetraosylceramide antibody resulted in a lethal infection, with enhancement of bacterial load in the lungs and dissemination of the bacteria to the liver via the blood. NK cell-depleted mice had significantly reduced B. pertussis-specific IFN-gamma and enhanced IgG1 and IL-5, but not IL-10 production, suggesting that regulatory T cells are induced simultaneously with Th1 cells, but the absence of NK cells resulted in enhancement of Th2-type responses. These findings suggest that NK cells confer resistance to B. pertussis by activating IL-12-mediated production of IFN-gamma, which enhances the anti-bacterial activity of macrophages, but also promotes the differentiation of Th1 cells.
  European Journal of Immunology 10/2004; 34(9):2579-88. · 5.10 Impact Factor
• Article: Toll-like receptor 4-mediated innate IL-10 activates antigen-specific regulatory T cells and confers resistance to Bordetella pertussis by inhibiting inflammatory pathology.

  Sarah C Higgins, Ed C Lavelle, Chantelle McCann, Brian Keogh, Edel McNeela, Patricia Byrne, Brian O'Gorman, Andrew Jarnicki, Peter McGuirk, Kingston H G Mills
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  ABSTRACT: Signaling through Toll-like receptors (TLR) activates dendritic cell (DC) maturation and IL-12 production, which directs the induction of Th1 cells. We found that the production of IL-10, in addition to inflammatory cytokines and chemokines, was significantly reduced in DCs from TLR4-defective C3H/HeJ mice in response to Bordetella pertussis. TLR4 was also required for B. pertussis LPS-induced maturation of DCs, but other B. pertussis components stimulated DC maturation independently of TLR4. The course of B. pertussis infection was more severe in C3H/HeJ than in C3H/HeN mice. Surprisingly, Ab- and Ag-specific IFN-gamma responses were enhanced at the peak of infection, whereas Ag-specific IL-10-producing T cells were significantly reduced in C3H/HeJ mice. This was associated with enhanced inflammatory cytokine production, cellular infiltration, and severe pathological changes in the lungs of TLR4-defective mice. Our findings suggest that TLR-4 signaling activates innate IL-10 production in response to B. pertussis, which both directly, and by promoting the induction of IL-10-secreting type 1 regulatory T cells, may inhibit Th1 responses and limit inflammatory pathology in the lungs during infection with B. pertussis.
  The Journal of Immunology 10/2003; 171(6):3119-27. · 5.79 Impact Factor