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Infection and Immunity, October 2009, p. 4567-4573, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00727-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Uncoupling Scavenger Receptor A-Mediated Phagocytosis of Bacteria from Endotoxic Shock Resistance {triangledown}

Eyal Amiel, Julie L. Acker, Ryan M. Collins, and Brent Berwin*

Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, New Hampshire 03756

Received 26 June 2009/ Returned for modification 28 July 2009/ Accepted 1 August 2009

Unresolved infection by gram-negative bacteria can result in the potentially lethal condition known as endotoxic shock, whereby uncontrolled inflammation can lead to multiple organ failure and death of the infected host. Previous results have demonstrated that animals deficient in class A scavenger receptor (SRA), a trafficking receptor for bacteria and bacterium-derived molecules, are more susceptible to endotoxic shock. This has been proposed to be a result of impaired SRA-dependent phagocytic clearance of bacteria resulting in stronger proinflammatory stimuli. In this report, we test the hypothesis that there is an obligate reciprocal relationship between SRA-mediated phagocytosis of bacteria and susceptibility to endotoxic shock. Here, we demonstrate that both SRA-dependent and -independent gram-negative bacterial strains elicit SRA-dependent increased cytokine production in vitro and in vivo and increased susceptibility to endotoxic shock in SRA-deficient mice. This is the first evidence showing that SRA-mediated clearance of LPS is functionally distinct from the role of SRA in bacterial phagocytosis and is a formal demonstration that the SRA-dependent cytokine responses and the resultant endotoxic shock are not coupled to SRA-mediated clearance of bacteria.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756. Phone: (603) 650-6899. Fax: (603) 650-6223. E-mail: berwin{at}dartmouth.edu

{triangledown} Published ahead of print on 10 August 2009.

Editor: A. Camilli


Infection and Immunity, October 2009, p. 4567-4573, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00727-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.