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  1. Article ; Online: Human MAIT Cells Respond to Staphylococcus aureus with Enhanced Anti-Bacterial Activity

    Andrew J. R. Cooper / Jonah Clegg / Féaron C. Cassidy / Andrew E. Hogan / Rachel M. McLoughlin

    Microorganisms, Vol 10, Iss 148, p

    2022  Volume 148

    Abstract: Mucosal-Associated Invariant T (MAIT) cells have been shown to play protective roles during infection with diverse pathogens through their propensity for rapid innate-like cytokine production and cytotoxicity. Among the potential applications for MAIT ... ...

    Abstract Mucosal-Associated Invariant T (MAIT) cells have been shown to play protective roles during infection with diverse pathogens through their propensity for rapid innate-like cytokine production and cytotoxicity. Among the potential applications for MAIT cells is to defend against Staphylococcus aureus , a pathogen of serious clinical significance. However, it is unknown how MAIT cell responses to S. aureus are elicited, nor has it been investigated whether MAIT cell cytotoxicity is mobilized against intracellular S. aureus . In this study, we investigate the capacity of human MAIT cells to respond directly to S. aureus . MAIT cells co-cultured with dendritic cells (DCs) infected with S. aureus rapidly upregulate CD69, express IFNγ and Granzyme B and degranulate. DC secretion of IL-12, but not IL-18, was implicated in this immune response, while TCR binding of MR1 is required to commence cytokine production. MAIT cell cytotoxicity resulted in apoptosis of S. aureus -infected cells, and reduced intracellular persistence of S. aureus . These findings implicate these unconventional T cells in important, rapid anti- S. aureus responses that may be of great relevance to the ongoing development of novel anti- S. aureus treatments.
    Keywords Staphylococcus aureus ; MAIT cell ; vaccines ; cell mediated immunity ; IFNγ ; dendritic cell ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Distinct receptor binding domain IgG thresholds predict protective host immunity across SARS-CoV-2 variants and time

    Grace Kenny / Sophie O’Reilly / Neil Wrigley Kelly / Riya Negi / Colette Gaillard / Dana Alalwan / Gurvin Saini / Tamara Alrawahneh / Nathan Francois / Matthew Angeliadis / Alejandro Abner Garcia Leon / Willard Tinago / Eoin R. Feeney / Aoife G. Cotter / Eoghan de Barra / Obada Yousif / Mary Horgan / Peter Doran / Jannik Stemler /
    Philipp Koehler / Rebecca Jane Cox / Donal O’Shea / Ole F. Olesen / Alan Landay / Andrew E. Hogan / Jean-Daniel Lelievre / Virginie Gautier / Oliver A. Cornely / Patrick W. G. Mallon / The All Ireland Infectious Diseases Cohort Study

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 11

    Abstract: Abstract SARS-CoV-2 neutralising antibodies provide protection against COVID-19. Evidence from early vaccine trials suggested binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether these thresholds predict ... ...

    Abstract Abstract SARS-CoV-2 neutralising antibodies provide protection against COVID-19. Evidence from early vaccine trials suggested binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether these thresholds predict sufficient neutralising capacity against variants of concern (VOCs), and whether this is impacted by vaccine or infection history remains unclear. Here we analyse individuals recovered from, vaccinated or with hybrid immunity against SARS-CoV-2. An NT50 ≥ 100 IU confers protection in vaccine trials, however, as VOC induce a reduction in NT50, we use NT50 ≥ 1000 IU as a cut off for WT NT50 that would retain neutralisation against VOC. In unvaccinated convalescent participants, a receptor binding domain (RBD) IgG of 456 BAU/mL predicts an NT50 against WT of 1000 IU with an accuracy of 80% (95%CI 73–86%). This threshold maintains accuracy in determining loss of protective immunity against VOC in two vaccinated cohorts. It predicts an NT50 < 100 IU against Beta with an accuracy of 80% (95%CI 67–89%) in 2 vaccine dose recipients. In booster vaccine recipients with a history of COVID-19 (hybrid immunity), accuracy is 87% (95%CI 77–94%) in determining an NT50 of <100 IU against BA.5. This analysis provides a discrete threshold that could be used in future clinical studies.
    Keywords Science ; Q
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction

    Eirini Giannoudaki / Yasmina E. Hernandez-Santana / Kelly Mulfaul / Sarah L. Doyle / Emily Hams / Padraic G. Fallon / Arimin Mat / Donal O’Shea / Manfred Kopf / Andrew E. Hogan / Patrick T. Walsh

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 14

    Abstract: IL-36α,β and ɣ are IL-1-related cytokines promoting inflammation in the skin and intestine. Here the authors show they are elevated in individuals with obesity, and that mice lacking the IL-36 receptor antagonist are more resistant to diet-induced ... ...

    Abstract IL-36α,β and ɣ are IL-1-related cytokines promoting inflammation in the skin and intestine. Here the authors show they are elevated in individuals with obesity, and that mice lacking the IL-36 receptor antagonist are more resistant to diet-induced obesity and metabolic dysfunction, which depends on intestinal microbiota.
    Keywords Science ; Q
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction

    Eirini Giannoudaki / Yasmina E. Hernandez-Santana / Kelly Mulfaul / Sarah L. Doyle / Emily Hams / Padraic G. Fallon / Arimin Mat / Donal O’Shea / Manfred Kopf / Andrew E. Hogan / Patrick T. Walsh

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 14

    Abstract: IL-36α,β and ɣ are IL-1-related cytokines promoting inflammation in the skin and intestine. Here the authors show they are elevated in individuals with obesity, and that mice lacking the IL-36 receptor antagonist are more resistant to diet-induced ... ...

    Abstract IL-36α,β and ɣ are IL-1-related cytokines promoting inflammation in the skin and intestine. Here the authors show they are elevated in individuals with obesity, and that mice lacking the IL-36 receptor antagonist are more resistant to diet-induced obesity and metabolic dysfunction, which depends on intestinal microbiota.
    Keywords Science ; Q
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

    Adriana J Michielsen / Andrew E Hogan / Joseph Marry / Miriam Tosetto / Fionnuala Cox / John M Hyland / Kieran D Sheahan / Diarmuid P O'Donoghue / Hugh E Mulcahy / Elizabeth J Ryan / Jacintha N O'Sullivan

    PLoS ONE, Vol 6, Iss 11, p e

    2011  Volume 27944

    Abstract: Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that ...

    Abstract Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616 ; 610
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Distinct and overlapping effector functions of expanded human CD4+, CD8α+ and CD4-CD8α- invariant natural killer T cells.

    Vincent O'Reilly / Shijuan G Zeng / Gabriel Bricard / Ann Atzberger / Andrew E Hogan / John Jackson / Conleth Feighery / Steven A Porcelli / Derek G Doherty

    PLoS ONE, Vol 6, Iss 12, p e

    2011  Volume 28648

    Abstract: CD1d-restricted invariant natural killer T (iNKT) cells have diverse immune stimulatory/regulatory activities through their ability to release cytokines and to kill or transactivate other cells. Activation of iNKT cells can protect against multiple ... ...

    Abstract CD1d-restricted invariant natural killer T (iNKT) cells have diverse immune stimulatory/regulatory activities through their ability to release cytokines and to kill or transactivate other cells. Activation of iNKT cells can protect against multiple diseases in mice but clinical trials in humans have had limited impact. Clinical studies to date have targeted polyclonal mixtures of iNKT cells and we proposed that their subset compositions will influence therapeutic outcomes. We sorted and expanded iNKT cells from healthy donors and compared the phenotypes, cytotoxic activities and cytokine profiles of the CD4(+), CD8α(+) and CD4(-)CD8α(-) double-negative (DN) subsets. CD4(+) iNKT cells expanded more readily than CD8α(+) and DN iNKT cells upon mitogen stimulation. CD8α(+) and DN iNKT cells most frequently expressed CD56, CD161 and NKG2D and most potently killed CD1d(+) cell lines and primary leukemia cells. All iNKT subsets released Th1 (IFN-γ and TNF-α) and Th2 (IL-4, IL-5 and IL-13) cytokines. Relative amounts followed a CD8α>DN>CD4 pattern for Th1 and CD4>DN>CD8α for Th2. All iNKT subsets could simultaneously produce IFN-γ and IL-4, but single-positivity for IFN-γ or IL-4 was strikingly rare in CD4(+) and CD8α(+) fractions, respectively. Only CD4(+) iNKT cells produced IL-9 and IL-10; DN cells released IL-17; and none produced IL-22. All iNKT subsets upregulated CD40L upon glycolipid stimulation and induced IL-10 and IL-12 secretion by dendritic cells. Thus, subset composition of iNKT cells is a major determinant of function. Use of enriched CD8α(+), DN or CD4(+) iNKT cells may optimally harness the immunoregulatory properties of iNKT cells for treatment of disease.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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