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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3588-3595. Prepublished online as a Blood First Edition Paper on December 16, 2004; DOI 10.1182/blood-2004-08-3251. This Article Full Text (PDF) All Versions of this Article: 2004-08-3251v1 105/9/3588    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Benjamim, C. F Articles by Kunkel, S. L Search for Related Content PubMed PubMed Citation Articles by Benjamim, C. F Articles by Kunkel, S. L Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 23, 2004 Accepted December 7, 2004 Reversal of long-term sepsis-induced immunosuppression by dendritic cell Claudia F Benjamim, Steven K Lundy, Nicholas W Lukacs, Cory M Hogaboam, and Steven L Kunkel* Department of Pathology, University of Michigan, Medical School, Ann Arbor, Michigan, USA * Corresponding author; email: slkunkel{at}umich.edu. Severe sepsis leads to long-term systemic and local immunosuppression, which is the cause of a number of complications, including pulmonary infection. A therapeutic strategy that reverses this immunosuppression is required, given the ongoing high mortality rate of patients that have survived a severe sepsis. The present study demonstrates that experimental severe sepsis renders the lung susceptible to a normally innocuous A. fumigatus fungus challenge, due to a dominant lung type-2 cytokine profile. Dendritic cells (DCs) obtained from lung of mice subjected to cecal ligation and puncture (CLP) model were skewed towards type 2 cytokine profile, which occurred with exaggerated expression of Toll-like receptor 2 (TLR2). The intrapulmonary transfer of bone-marrow derived DCs (BMDCs) in post-septic mice prevented fatal Aspergillus infection. This therapy reduced the overall inflammatory response, fungal growth in the lung and promote the balance of pro-inflamatory and supressive-cytokines in the lung. Thus, intrapulmonary DC supplementation appears to restore the pulmonary host response in the post-septic lung in our animal model. This data strongly suggests lung DCs are profoundly affected as a consequence of the systemic impact of severe sepsis and the identification of mechanisms that restore their function may serve as a key strategy to reverse sepsis-induced immunosuppression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Pene, B. Zuber, E. Courtine, C. Rousseau, F. Ouaaz, J. Toubiana, A. Tazi, J.-P. Mira, and J.-D. Chiche Dendritic Cells Modulate Lung Response to Pseudomonas aeruginosa in a Murine Model of Sepsis-Induced Immune Dysfunction J. Immunol., December 15, 2008; 181(12): 8513 - 8520. [Abstract] [Full Text] [PDF] G. Plitas, B. M. Burt, H. M. Nguyen, Z. M. Bamboat, and R. P. DeMatteo Toll-like receptor 9 inhibition reduces mortality in polymicrobial sepsis J. Exp. Med., June 9, 2008; 205(6): 1277 - 1283. [Abstract] [Full Text] [PDF] H. Wen, M. A. Schaller, Y. Dou, C. M. Hogaboam, and S. L. Kunkel Dendritic cells at the interface of innate and acquired immunity: the role for epigenetic changes J. Leukoc. Biol., March 1, 2008; 83(3): 439 - 446. [Abstract] [Full Text] [PDF] H. Wen, Y. Dou, C. M. Hogaboam, and S. L. Kunkel Epigenetic regulation of dendritic cell-derived interleukin-12 facilitates immunosuppression after a severe innate immune response Blood, February 15, 2008; 111(4): 1797 - 1804. [Abstract] [Full Text] [PDF] H. Wen, C. M. Hogaboam, J. Gauldie, and S. L. Kunkel Severe Sepsis Exacerbates Cell-Mediated Immunity in the Lung Due to an Altered Dendritic Cell Cytokine Profile Am. J. Pathol., June 1, 2006; 168(6): 1940 - 1950. [Abstract] [Full Text] [PDF] S. B. Flohe, H. Agrawal, D. Schmitz, M. Gertz, S. Flohe, and F. U. Schade Dendritic cells during polymicrobial sepsis rapidly mature but fail to initiate a protective Th1-type immune response J. Leukoc. Biol., March 1, 2006; 79(3): 473 - 481. [Abstract] [Full Text] [PDF] S. Knapp, C. W. Wieland, S. Florquin, R. Pantophlet, L. Dijkshoorn, N. Tshimbalanga, S. Akira, and T. van der Poll Differential Roles of CD14 and Toll-like Receptors 4and 2 in Murine Acinetobacter Pneumonia Am. J. Respir. Crit. Care Med., January 1, 2006; 173(1): 122 - 129. [Abstract] [Full Text] [PDF] K. J. Carpenter and C. M. Hogaboam Immunosuppressive Effects of CCL17 on Pulmonary Antifungal Responses during Pulmonary Invasive Aspergillosis Infect. Immun., November 1, 2005; 73(11): 7198 - 7207. [Abstract] [Full Text] [PDF]

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