| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
* Department of Environmental Health Sciences,
Department of Pathology, and
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University, Bloomberg School of Public Health and School of Medicine, Baltimore, MD 21205
Recent clinical studies have reinforced the importance of sex-related differences in the pathogenesis of cardiovascular diseases, with an increased incidence and mortality in men. Similar to humans, male BALB/c mice infected with coxsackievirus B3 (CVB3) develop more severe inflammation in the heart even though viral replication is no greater than in females. We show that TLR4 and IFN-
levels are significantly elevated and regulatory T cell (Treg) populations significantly reduced in the heart of males following CVB3 infection, whereas females have significantly increased T cell Ig mucin (Tim)-3, IL-4 and Treg. Blocking Tim-3 in males significantly increases inflammation and TLR4 expression while reducing Treg. In contrast, defective TLR4 signaling significantly reduces inflammation while increasing Tim-3 expression. Cross-regulation of TLR4 and Tim-3 occurs during the innate and adaptive immune response. This novel mechanism may help explain why inflammatory heart disease is more severe in males.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants HL087033 (to D.F.), HL70729 and HL077611 (to N.R.R.), T32 ES07141 (to J.F.N.) and ES03819.
2 Address correspondence and reprint requests to Dr. DeLisa Fairweather, Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, 615 N. Wolfe Street, Rm. E7628, Baltimore, MD 21205. Ph: 410-955-4712; Fax: 410-955-0116; E-mail: dfairwea{at}jhsph.edu
3 Abbreviations used in this paper: CVB3, coxsackievirus B3; DC, dendritic cells; Foxp3, forkhead box p3; MC, mast cells; p.i., postinfection; Tim-3, T cell Ig mucin-3; Treg, regulatory T cells.
This article has been cited by other articles:
|
|
 |
|
  L. T. Cooper Jr. Myocarditis N. Engl. J. Med., April 9, 2009; 360(15): 1526 - 1538. [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Dube, D. Fairweather, W. S. Pearson, V. J. Felitti, R. F. Anda, and J. B. Croft Cumulative Childhood Stress and Autoimmune Diseases in Adults Psychosom Med, February 1, 2009; 71(2): 243 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fairweather, S. Frisancho-Kiss, and N. R. Rose Sex Differences in Autoimmune Disease from a Pathological Perspective Am. J. Pathol., September 1, 2008; 173(3): 600 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Riad, S. Jager, M. Sobirey, F. Escher, A. Yaulema-Riss, D. Westermann, A. Karatas, M. M. Heimesaat, S. Bereswill, D. Dragun, et al. Toll-Like Receptor-4 Modulates Survival by Induction of Left Ventricular Remodeling after Myocardial Infarction in Mice J. Immunol., May 15, 2008; 180(10): 6954 - 6961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Jane-wit, C. Z. Altuntas, J. Monti, J. M. Johnson, T. G. Forsthuber, and V. K. Tuohy Sex-Defined T-Cell Responses to Cardiac Self Determine Differential Outcomes of Murine Dilated Cardiomyopathy Am. J. Pathol., January 1, 2008; 172(1): 11 - 21. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
