Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderly

被引：120

作者：

Qian, Feng ^{[1
]}

Wang, Xiaomei ^{[1
]}

Zhang, Lin ^{[1
]}

Chen, Shu ^{[2
]}

Piecychna, Marta ^{[1
]}

Allore, Heather ^{[2
]}

Bockenstedt, Linda ^{[1
]}

Malawista, Stephen ^{[1
]}

Bucala, Richard ^{[1
]}

Shaw, Albert C. ^{[3
]}

Fikrig, Erol ^{[3
,4
]}

Montgomery, Ruth R. ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Internal Med, Rheumatol Sect, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Dept Internal Med, Program Aging, New Haven, CT 06520 USA

[3] Yale Univ, Sch Med, Dept Internal Med, Infect Dis Sect, New Haven, CT 06520 USA

[4] Howard Hughes Med Inst, New Haven, CT 06520 USA

来源：

AGING CELL | 2012年 / 11卷 / 01期

关键词：

aging; toll-like receptors; monocytes; immunosenescence; IL-8; flagellin; MIGRATION INHIBITORY FACTOR; INFLUENZA VACCINE; DENDRITIC CELLS; IMMUNE-RESPONSE; FLAGELLIN; EXPRESSION; INNATE; TOLL-LIKE-RECEPTOR-5; IMMUNOSENESCENCE; INTERLEUKIN-8;

D O I：

10.1111/j.1474-9726.2011.00759.x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Aging is accompanied by a progressive decline in immune function. Studies have shown age-related decreases in the expression and signaling efficiency of Toll-like receptors (TLRs) in monocytes and dendritic cells and dysregulation of macrophage TLR3. Using a multivariable mixed effect model, we report a highly significant increase in TLR5-induced production of IL-8 from monocytes of older individuals (P < 0.0001). Elevated IL-8 is accompanied by increased expression of TLR5, both protein and mRNA, and by increased levels of TLR5-mediated phosphorylation of MAPK p38 and ERK. We noted incomplete activation of NF-?B in response to TLR5 signaling in monocytes of elderly donors, as reflected by the absence of an associated increase in the production of TNF-a. Elevated TLR5 may provide a critical mechanism to enhance immune responsiveness in older individuals.

引用

页码：104 / 110

页数：7

共 40 条

[1] TLR accessory molecules [J].

Akashi-Takamura, Sachiko ;

Miyake, Kensuke .

CURRENT OPINION IN IMMUNOLOGY, 2008, 20 (04) :420-425

[2] Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice [J].

Alexopoulou, L ;

Thomas, V ;

Schnare, M ;

Lobet, Y ;

Anguita, J ;

Schoen, RT ;

Medzhitov, R ;

Fikrig, E ;

Flavell, RA .

NATURE MEDICINE, 2002, 8 (08) :878-884

[3] Mucosal adjuvant activity of flagellin in aged mice [J].

Bates, John T. ;

Honko, Anna N. ;

Graff, Aaron H. ;

Kock, Nancy D. ;

Mizel, Steven B. .

MECHANISMS OF AGEING AND DEVELOPMENT, 2008, 129 (05) :271-281

[4] An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models [J].

Burdelya, Lyudmila G. ;

Krivokrysenko, Vadim I. ;

Tallant, Thomas C. ;

Strom, Evguenia ;

Gleiberman, Anatoly S. ;

Gupta, Damodar ;

Kurnasov, Oleg V. ;

Fort, Farrel L. ;

Osterman, Andrei L. ;

DiDonato, Joseph A. ;

Feinstein, Elena ;

Gudkov, Andrei V. .

SCIENCE, 2008, 320 (5873) :226-230

[5] Immunodeficiency: UNC-93B gets a toll call [J].

Conley, Mary Ellen .

TRENDS IN IMMUNOLOGY, 2007, 28 (03) :99-101

[6] Antigen-Containing Liposomes Engrafted with Flagellin-Related Peptides Are Effective Vaccines That Can Induce Potent Antitumor Immunity and Immunotherapeutic Effect [J].

Faham, Abdus ;

Altin, Joseph G. .

JOURNAL OF IMMUNOLOGY, 2010, 185 (03) :1744-1754

[7] Randomized, Double-Blind Controlled Phase 3 Trial Comparing the Immunogenicity of High-Dose and Standard-Dose Influenza Vaccine in Adults 65 Years of Age and Older [J].

Falsey, Ann R. ;

Treanor, John J. ;

Tornieporth, Nadia ;

Capellan, Jose ;

Gorse, Geoffrey J. .

JOURNAL OF INFECTIOUS DISEASES, 2009, 200 (02) :172-180

[8] Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria [J].

Feuillet, Vincent ;

Medjane, Samir ;

Mondor, Isabelle ;

Demaria, Olivier ;

Pagni, Philippe P. ;

Galan, Jorge E. ;

Flavell, Richard A. ;

Alexopoulou, Lena .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (33) :12487-12492

[9] Inflammaging and anti-inflammaging: A systemic perspective on aging and longevity emerged from studies in humans [J].

Franceschi, Claudio ;

Capri, Miriam ;

Monti, Daniela ;

Giunta, Sergio ;

Olivieri, Fabiola ;

Sevini, Federica ;

Panouraia, Maria Panagiota ;

Invidia, Laura ;

Celani, Laura ;

Scurti, Maria ;

Cevenini, Elisa ;

Castellani, Gastone C. ;

Salvioli, Stefano .

MECHANISMS OF AGEING AND DEVELOPMENT, 2007, 128 (01) :92-105

[10]

Hoffmann E, 2002, J LEUKOCYTE BIOL, V72, P847

← 1 2 3 4 →