| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Cutting Edge |
* Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; and
Department of Pathology, Emory University, Atlanta, GA 30322
Toll-like receptors (TLR) are pattern recognition receptors that
recognize conserved molecular patterns on microbes and link innate and
adaptive immune systems. We investigated whether the enhanced
susceptibility to bacterial, yeast, and viral infections and poor
adaptive immune responses in aging are a result of diminished
expression and function of TLRs. We examined the expression and
function of all murine TLRs on macrophages from young and aged mice.
Both splenic and activated peritoneal macrophages from aged mice
expressed significantly lower levels of all TLRs. Furthermore,
macrophages from aged mice secreted significantly lower levels of IL-6
and TNF-
when stimulated with known ligands for TLR1 and 2, 2 and
6,TLR3, TLR4, TLR5, and TLR9 when compared with those from young mice.
These results support the concept that increased susceptibility to
infections and poor adaptive immune responses in aging may be due to
the decline in TLR expression and function.
This article has been cited by other articles:
|
|
 |
|
  Z. Ren, R. Gay, A. Thomas, M. Pae, D. Wu, L. Logsdon, J. Mecsas, and S. N. Meydani Effect of age on susceptibility to Salmonella Typhimurium infection in C57BL/6 mice J. Med. Microbiol., December 1, 2009; 58(12): 1559 - 1567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Agius, K. E. Lacy, M. Vukmanovic-Stejic, A. L. Jagger, A.-P. Papageorgiou, S. Hall, J. R. Reed, S. J. Curnow, J. Fuentes-Duculan, C. D. Buckley, et al. Decreased TNF-{alpha} synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging J. Exp. Med., August 31, 2009; 206(9): 1929 - 1940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Swain and J. Nikolich-Zugich Key Research Opportunities in Immune System Aging J Gerontol A Biol Sci Med Sci, February 27, 2009; (2009) gln068v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-C. Chiu, V. R. Stolberg, and S. W. Chensue Mononuclear Phagocyte-Derived IL-10 Suppresses the Innate IL-12/IFN-{gamma} Axis in Lung-Challenged Aged Mice J. Immunol., September 1, 2008; 181(5): 3156 - 3166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-F. Kong, K. Delroux, X. Wang, F. Qian, A. Arjona, S. E. Malawista, E. Fikrig, and R. R. Montgomery Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly J. Virol., August 1, 2008; 82(15): 7613 - 7623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bujak, H. J. Kweon, K. Chatila, N. Li, G. Taffet, and N. G. Frangogiannis Aging-Related Defects Are Associated With Adverse Cardiac Remodeling in a Mouse Model of Reperfused Myocardial Infarction J. Am. Coll. Cardiol., April 8, 2008; 51(14): 1384 - 1392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Albert and J. S. Marshall Aging in the absence of TLR2 is associated with reduced IFN-{gamma} responses in the large intestine and increased severity of induced colitis J. Leukoc. Biol., April 1, 2008; 83(4): 833 - 842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-C. Chiu, V. R. Stolberg, C. M. Freeman, and S. W. Chensue Mononuclear Phagocyte-Derived Interleukin-10 Suppresses the Innate Pulmonary Granuloma Cytokine Response in Aged Mice Am. J. Pathol., September 1, 2007; 171(3): 829 - 837. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Agrawal, S. Agrawal, J.-N. Cao, H. Su, K. Osann, and S. Gupta Altered Innate Immune Functioning of Dendritic Cells in Elderly Humans: A Role of Phosphoinositide 3-Kinase-Signaling Pathway J. Immunol., June 1, 2007; 178(11): 6912 - 6922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Blaise, N. Vey, C. Faucher, and M. Mohty Current status of reduced intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia Haematologica, April 1, 2007; 92(4): 533 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. van Duin, S. Mohanty, V. Thomas, S. Ginter, R. R. Montgomery, E. Fikrig, H. G. Allore, R. Medzhitov, and A. C. Shaw Age-Associated Defect in Human TLR-1/2 Function J. Immunol., January 15, 2007; 178(2): 970 - 975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Murciano, E. Villamon, A. Yanez, J.-E. O'Connor, D. Gozalbo, and M. L. Gil Impaired immune response to Candida albicans in aged mice. J. Med. Microbiol., December 1, 2006; 55(Pt 12): 1649 - 1656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Boyd, S. Mathur, Y. Wang, R. M. Bateman, and K. R. Walley Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-{kappa}B dependent inflammatory response Cardiovasc Res, December 1, 2006; 72(3): 384 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Chelvarajan, Y. Liu, D. Popa, M. L. Getchell, T. V. Getchell, A. J. Stromberg, and S. Bondada Molecular basis of age-associated cytokine dysregulation in LPS-stimulated macrophages J. Leukoc. Biol., June 1, 2006; 79(6): 1314 - 1327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Ujvari and T. Madsen Age, parasites, and condition affect humoral immune response in tropical pythons Behav. Ecol., January 1, 2006; 17(1): 20 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Guo, S. Garg, K. M. Hill, L. Jayashankar, M. R. Mooney, M. Hoelscher, J. M. Katz, J. M. Boss, and S. Sambhara A Distal Regulatory Region Is Required for Constitutive and IFN-{beta}-Induced Expression of Murine TLR9 Gene J. Immunol., December 1, 2005; 175(11): 7407 - 7418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jiang, D. Gross, S. Nogusa, P. Elbaum, and D. M. Murasko Depletion of T Cells by Type I Interferon: Differences between Young and Aged Mice J. Immunol., August 1, 2005; 175(3): 1820 - 1826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Roberts, C. Paddock, L. Vogel, E. Butler, S. Zaki, and K. Subbarao Aged BALB/c Mice as a Model for Increased Severity of Severe Acute Respiratory Syndrome in Elderly Humans J. Virol., May 1, 2005; 79(9): 5833 - 5838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Chelvarajan, S. M. Collins, J. M. Van Willigen, and S. Bondada The unresponsiveness of aged mice to polysaccharide antigens is a result of a defect in macrophage function J. Leukoc. Biol., April 1, 2005; 77(4): 503 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. I Lancaster, Q. Khan, P. Drysdale, F. Wallace, A. E Jeukendrup, M. T Drayson, and M. Gleeson The physiological regulation of toll-like receptor expression and function in humans J. Physiol., March 15, 2005; 563(3): 945 - 955. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. VanderMeer, Q. Sha, A. P. Lane, and R. P. Schleimer Innate Immunity of the Sinonasal Cavity: Expression of Messenger RNA for Complement Cascade Components and Toll-like Receptors Arch Otolaryngol Head Neck Surg, December 1, 2004; 130(12): 1374 - 1380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Pioli, E. Amiel, T. M. Schaefer, J. E. Connolly, C. R. Wira, and P. M. Guyre Differential Expression of Toll-Like Receptors 2 and 4 in Tissues of the Human Female Reproductive Tract Infect. Immun., October 1, 2004; 72(10): 5799 - 5806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Fayad, H. Zhang, D. Quinn, Y. Huang, and L. Qiao Oral Administration with Papillomavirus Pseudovirus Encoding IL-2 Fully Restores Mucosal and Systemic Immune Responses to Vaccinations in Aged Mice J. Immunol., August 15, 2004; 173(4): 2692 - 2698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. P. Plackett, E. D. Boehmer, D. E. Faunce, and E. J. Kovacs Aging and innate immune cells J. Leukoc. Biol., August 1, 2004; 76(2): 291 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Kovacs, T. P. Plackett, and P. L. Witte Estrogen replacement, aging, and cell-mediated immunity after injury J. Leukoc. Biol., July 1, 2004; 76(1): 36 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Didierlaurent, I. Ferrero, L. A. Otten, B. Dubois, M. Reinhardt, H. Carlsen, R. Blomhoff, S. Akira, J.-P. Kraehenbuhl, and J.-C. Sirard Flagellin Promotes Myeloid Differentiation Factor 88-Dependent Development of Th2-Type Response J. Immunol., June 1, 2004; 172(11): 6922 - 6930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cuadros, F. J. Lopez-Hernandez, A. L. Dominguez, M. McClelland, and J. Lustgarten Flagellin Fusion Proteins as Adjuvants or Vaccines Induce Specific Immune Responses Infect. Immun., May 1, 2004; 72(5): 2810 - 2816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Frasca, E. Van der Put, R. L. Riley, and B. B. Blomberg Reduced Ig Class Switch in Aged Mice Correlates with Decreased E47 and Activation-Induced Cytidine Deaminase J. Immunol., February 15, 2004; 172(4): 2155 - 2162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Kurt-Jones, M. Chan, S. Zhou, J. Wang, G. Reed, R. Bronson, M. M. Arnold, D. M. Knipe, and R. W. Finberg Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis PNAS, February 3, 2004; 101(5): 1315 - 1320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Boehmer, J. Goral, D. E. Faunce, and E. J. Kovacs Age-dependent decrease in Toll-like receptor 4-mediated proinflammatory cytokine production and mitogen-activated protein kinase expression J. Leukoc. Biol., February 1, 2004; 75(2): 342 - 349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Janssens and R. Beyaert Role of Toll-Like Receptors in Pathogen Recognition Clin. Microbiol. Rev., October 1, 2003; 16(4): 637 - 646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Davenport Immunity Challenge Sci. Aging Knowl. Environ., June 11, 2003; 2003(23): oa1 - 1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Means, F. Hayashi, K. D. Smith, A. Aderem, and A. D. Luster The Toll-Like Receptor 5 Stimulus Bacterial Flagellin Induces Maturation and Chemokine Production in Human Dendritic Cells J. Immunol., May 15, 2003; 170(10): 5165 - 5175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wu, M. Marko, K. Claycombe, K. E. Paulson, and S. N. Meydani Ceramide-induced and Age-associated Increase in Macrophage COX-2 Expression Is Mediated through Up-regulation of NF-kappa B Activity J. Biol. Chem., March 21, 2003; 278(13): 10983 - 10992. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
