Diminished responsiveness to human β-defensin-3 and decreased TLR1 expression on monocytes and mDCs from HIV-1-infected patients

Journal of Leukocyte Biology

Scott F. Sieg, ²  Nicholas T. Funderburg¹  *¹  Scott F. Sieg¹  Nicholas T. Funderburg, and² 

[1] Department of Medicine, Division of Infectious Diseases, Case Western Reserve University/University Hospitals of Cleveland, and Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA Department of Medicine, Division of Infectious Diseases, Case Western Reserve University/University Hospitals of Cleveland, and Department of Medicine, Division of Infectious Diseases, Case Western Reserve University/University Hospitals of Cleveland, and Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA Department of Medicine, Division of Infectious Diseases, Case Western Reserve University/University Hospitals of Cleveland, and Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA;Department of Medicine, Division of Infectious Diseases, Case Western Reserve University/University Hospitals of Cleveland, and  Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA

关键词: antimicrobial peptide;    pattern recognition receptor;    costimulatory molecule;    antigen-presenting cell;   

DOI  :  10.1189/jlb.1111555

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

hBD-3 is an antimicrobial peptide that may contribute to adaptive immune responses by activating professional APCs via a TLR1/2-dependent mechanism. Patients with HIV disease experience increased susceptibility to mucosal infections, which may, in part, stem from diminished APC function. Our current studies demonstrate a reduced capacity of hBD-3 to induce the expression of a costimulatory molecule, CD80, on monocytes and mDCs from HIV-infected persons compared with cells from healthy controls. Although the expression of TLR1 and TLR2 on monocytes was not a strong predictor of hBD-3 responsiveness in bivariate analyses, monocytes and mDCs from HIV-infected persons expressed significantly lower levels of TLR1. Monocyte expression of the activation marker CD69, in cells from HIV-infected persons with therapeutically controlled viremia, was correlated directly with TLR2 and TLR4 expression but not with TLR1 expression. Overall, these studies suggest that immune activation may affect TLR2 and TLR4 expression but may not fully account for reduced TLR1 expression in monocytes from HIV-infected persons. Impairments in hBD-3 responsiveness and TLR1 expression are likely to contribute to increased risk of mucosal infection in HIV disease.

【 授权许可】

Unknown