TLR2-induced cytokine responses may characterize HIV-infected patients experiencing mycobacterial immune restoration disease
Objectives: Most HIV patients who experience Mycobacterium tuberculosis-associated immune restoration disease (TB IRD) display elevated interferon-gamma (IFN?) responses against mycobacterial antigens, but these can occur without an IRD. Recognition of mycobacteria-associated molecular patterns thro...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
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2011
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| Online Access: | http://hdl.handle.net/20.500.11937/29064 |
| _version_ | 1848752703300173824 |
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| author | Tan, D. Lim, A. Yong, Y. Ponnampalavanar, S. Omar, S. Kamarulzaman, A. French, M. Price, Patricia |
| author_facet | Tan, D. Lim, A. Yong, Y. Ponnampalavanar, S. Omar, S. Kamarulzaman, A. French, M. Price, Patricia |
| author_sort | Tan, D. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Objectives: Most HIV patients who experience Mycobacterium tuberculosis-associated immune restoration disease (TB IRD) display elevated interferon-gamma (IFN?) responses against mycobacterial antigens, but these can occur without an IRD. Recognition of mycobacteria-associated molecular patterns through toll-like receptors (TLRs) on dendritic cells and monocytes induces cytokine production. Here, we investigate TLR-induced responses in IRD. Design: Peripheral blood mononuclear cells (PBMCs) were collected at approximately weeks 0, 6, 12, 24 and 48 after antiretroviral therapy from five patients experiencing TB IRD, nine matched non-IRD patients and 15 healthy controls. Methods: IFN? production by PBMC stimulated with protein purified derivative (PPD) was assessed by ELISpot. TLR2 expression on myeloid dendritic cells (mDCs) and monocytes was assessed by flow cytometry. TNFa, IL-12p40 and IL-10 were measured by ELISA in 24-h cultures of PBMC with lipomannan (mycobacteria-derived TLR2 agonist). Results: TLR2 expression on mDC and monocytes was higher in patients than controls at baseline (P<0.005). TLR2 expression decreased to normal levels on mDC by week 12, but remained higher on monocytes at week 24 (P=0.02). At week 24, IRD patients showed higher IFN? responses to PPD (P=0.02), TLR2 expression on monocytes (P=0.006) and lipomannan-induced TNFa production (P=0.016) than non-IRD patients. Lipomannan-induced TNFa and IL-12p40 responses paralleled TB IRD in the patients with high TLR2 expression. IL-10 levels did not associate with IRD. Conclusion: TLR2-induced pro-inflammatory cytokines by dendritic cells or monocytes may contribute to the pathogenesis of mycobacterial IRD. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. |
| first_indexed | 2025-11-14T08:12:50Z |
| format | Journal Article |
| id | curtin-20.500.11937-29064 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:12:50Z |
| publishDate | 2011 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-290642017-09-13T15:24:46Z TLR2-induced cytokine responses may characterize HIV-infected patients experiencing mycobacterial immune restoration disease Tan, D. Lim, A. Yong, Y. Ponnampalavanar, S. Omar, S. Kamarulzaman, A. French, M. Price, Patricia Objectives: Most HIV patients who experience Mycobacterium tuberculosis-associated immune restoration disease (TB IRD) display elevated interferon-gamma (IFN?) responses against mycobacterial antigens, but these can occur without an IRD. Recognition of mycobacteria-associated molecular patterns through toll-like receptors (TLRs) on dendritic cells and monocytes induces cytokine production. Here, we investigate TLR-induced responses in IRD. Design: Peripheral blood mononuclear cells (PBMCs) were collected at approximately weeks 0, 6, 12, 24 and 48 after antiretroviral therapy from five patients experiencing TB IRD, nine matched non-IRD patients and 15 healthy controls. Methods: IFN? production by PBMC stimulated with protein purified derivative (PPD) was assessed by ELISpot. TLR2 expression on myeloid dendritic cells (mDCs) and monocytes was assessed by flow cytometry. TNFa, IL-12p40 and IL-10 were measured by ELISA in 24-h cultures of PBMC with lipomannan (mycobacteria-derived TLR2 agonist). Results: TLR2 expression on mDC and monocytes was higher in patients than controls at baseline (P<0.005). TLR2 expression decreased to normal levels on mDC by week 12, but remained higher on monocytes at week 24 (P=0.02). At week 24, IRD patients showed higher IFN? responses to PPD (P=0.02), TLR2 expression on monocytes (P=0.006) and lipomannan-induced TNFa production (P=0.016) than non-IRD patients. Lipomannan-induced TNFa and IL-12p40 responses paralleled TB IRD in the patients with high TLR2 expression. IL-10 levels did not associate with IRD. Conclusion: TLR2-induced pro-inflammatory cytokines by dendritic cells or monocytes may contribute to the pathogenesis of mycobacterial IRD. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. 2011 Journal Article http://hdl.handle.net/20.500.11937/29064 10.1097/QAD.0b013e328348fb18 unknown |
| spellingShingle | Tan, D. Lim, A. Yong, Y. Ponnampalavanar, S. Omar, S. Kamarulzaman, A. French, M. Price, Patricia TLR2-induced cytokine responses may characterize HIV-infected patients experiencing mycobacterial immune restoration disease |
| title | TLR2-induced cytokine responses may characterize HIV-infected patients experiencing mycobacterial immune restoration disease |
| title_full | TLR2-induced cytokine responses may characterize HIV-infected patients experiencing mycobacterial immune restoration disease |
| title_fullStr | TLR2-induced cytokine responses may characterize HIV-infected patients experiencing mycobacterial immune restoration disease |
| title_full_unstemmed | TLR2-induced cytokine responses may characterize HIV-infected patients experiencing mycobacterial immune restoration disease |
| title_short | TLR2-induced cytokine responses may characterize HIV-infected patients experiencing mycobacterial immune restoration disease |
| title_sort | tlr2-induced cytokine responses may characterize hiv-infected patients experiencing mycobacterial immune restoration disease |
| url | http://hdl.handle.net/20.500.11937/29064 |