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Aberrant Inflammaso...
Aberrant Inflammasome Activation Characterizes Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome
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- Yien Tan, Hong (författare)
- University of Malaya, Malaysia
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- Kong Yong, Yean (författare)
- University of Malaya, Malaysia
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- Shankar, Esaki M. (författare)
- University of Malaya, Malaysia; University of Malaya, Malaysia
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- Paukovics, Geza (författare)
- Macfarlane Burnet Institute Medical Research and Public Heatlh, Australia
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- Ellegård, Rada (författare)
- Linköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Medicinska fakulteten
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- Larsson, Marie (författare)
- Linköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Medicinska fakulteten
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- Kamarulzaman, Adeeba (författare)
- University of Malaya, Malaysia
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- French, Martyn A. (författare)
- University of Western Australia, Australia; Royal Perth Hospital, Australia
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- Crowe, Suzanne M. (författare)
- Macfarlane Burnet Institute Medical Research and Public Heatlh, Australia; Alfred Hospital, Australia; Monash University, Australia
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(creator_code:org_t)
- 2016-05-15
- 2016
- Engelska.
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Ingår i: Journal of Immunology. - : AMER ASSOC IMMUNOLOGISTS. - 0022-1767 .- 1550-6606. ; 196:10, s. 4052-4063
- Relaterad länk:
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https://www.jimmunol...
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https://urn.kb.se/re...
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https://doi.org/10.4...
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Abstract
Ämnesord
Stäng
- Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) complicates combination antiretroviral therapy (cART) in up to 25% of patients with HIV/TB coinfection. Monocytes and IL-18, a signature cytokine of inflammasome activation, are implicated in TB-IRIS pathogenesis. In this study, we investigated inflammasome activation both pre- and post-cART in TB-IRIS patients. HIV/TB patients exhibited higher proportions of monocytes expressing activated caspase-1 (casp1) pre-cART, compared with HIV patients without TB, and patients who developed TB-IRIS exhibited the greatest increase in casp1 expression. CD64(+) monocytes were a marker of increased casp1 expression. Furthermore, IL-1 beta, another marker of inflammasome activation, was also elevated during TB-IRIS. TB-IRIS patients also exhibited greater upregulation of NLRP3 and AIM2 inflammasome mRNA, compared with controls. Analysis of plasma mitochondrial DNA levels showed that TB-IRIS patients experienced greater cell death, especially pre-cART. Plasma NO levels were lower both pre- and post-cART in TB-IRIS patients, providing evidence of inadequate inflammasome regulation. Plasma IL-18 levels pre-cART correlated inversely with NO levels but positively with monocyte casp1 expression and mitochondrial DNA levels, and expression of IL-18R alpha on CD4(+) T cells and NK cells was higher in TB-IRIS patients, providing evidence that IL-18 is a marker of inflammasome activation. We propose that inflammasome activation in monocytes/macrophages of HIV/TB patients increases with ineffective T cell-dependent activation of monocytes/macrophages, priming them for an excessive inflammatory response after cART is commenced, which is greatest in patients with TB-IRIS.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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