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Systemic Tumor Necrosis Factor Generated during Lethal Plasmodium Infections Impairs Dendritic Cell Function¹

Michelle N. Wykes^*, Xue Q. Liu^*, Suhua Jiang^*,, Chakrit Hirunpetcharat^*, and Michael F. Good^2,*

^* The Molecular Immunology Laboratory, The Queensland Institute of Medical Research, The Bancroft Centre, Brisbane, Queensland, Australia; Department of Pathogenic Biology and Immunology, Shihezi University School of Medicine, Shihezi, Xinjiang Autonomous Region, People’s Republic of China; and Department of Microbiology, Faculty of Public Health, Mahidol University, Bangkok, Thailand

Dendritic cells (DCs) initiate innate and adaptive immune responses including those against malaria. Although several studies have shown that DC function is normal during malaria, other studies have shown compromised function. To establish why these studies had different findings, we examined DCs from mice infected with two lethal species of parasite, Plasmodium berghei or P. vinckei, and compared them to DCs from nonlethal P. yoelii 17XNL or P. chabaudi infections. These studies found that DCs from only the lethal infections became uniformly mature 7 days after infection and were functionally impaired as they were unable to endocytose latex particles, secrete IL-12, or present OVA to transgenic OTII T cells. These changes coincided with a peak in levels of systemic TNF-. Because TNF- is known to mature DCs, we used TNF-KO mice to determine the role of this cytokine in the loss of DC function. In the TNF-KO mice, phenotype, Ag presentation, and IL-12 secretion by DCs were restored to normal following both lethal infections. This study shows that the systemic production of TNF- contributes to poor DC function during lethal infections. These studies may explain, at least in part, immunosuppression that is associated with malaria.

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 the National Health and Medical Research Council. S.J. was supported by the China Scholarship Council.

² Address correspondence and reprint requests to Dr. Michael F. Good, Queensland Institute of Medical Research, Bancroft Centre, 300 Herston Road, Brisbane, Queensland, Australia. E-mail address: Michael.Good{at}qimr.edu.au

³ Abbreviations used in this paper: DC, dendritic cell; KO, knockout; WT, wild type.

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				K. A. Wong and A. Rodriguez Plasmodium Infection and Endotoxic Shock Induce the Expansion of Regulatory Dendritic Cells J. Immunol., January 15, 2008; 180(2): 716 - 726. [Abstract] [Full Text] [PDF]