TLR2-induced cytokine responses may characterize HIV-infected patients experiencing mycobacterial immune restoration disease

Tan, Dino B.A. and Lim, Andrew and Yean, K. Yong and Ponnampalavanar, Sasheela and Omar, Sharifah Faridah Syed and Kamarulzaman, Adeeba and French, Martyn A. and Price, Patricia (2011) TLR2-induced cytokine responses may characterize HIV-infected patients experiencing mycobacterial immune restoration disease. AIDS, 25 (12). pp. 1455-1460. ISSN 0269-9370

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Objectives: Most HIV patients who experience Mycobacterium tuberculosis-associated immune restoration disease (TB IRD) display elevated interferon-gamma (IFN gamma) 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: IFNg 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 flowcytometry. TNF alpha, 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 IFNg responses to PPD (P=0.02), TLR2 expression on monocytes (P=0.006) and lipomannan-induced TNF alpha production (P=0.016) than non-IRD patients. Lipomannan-induced TNF alpha 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. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Item Type: Article
Additional Information: Tan, Dino B. A. Lim, Andrew Yong, Yean K. Ponnampalavanar, Sasheela Omar, Sharifah Kamarulzaman, Adeeba French, Martyn A. Price, Patricia
Uncontrolled Keywords: dendritic cells; HIV; IRD; lipomannan; monocytes; TB-IRIS; TLR
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms azrahani halim
Date Deposited: 29 Jan 2013 03:40
Last Modified: 18 Nov 2019 07:39

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