Published ahead of print on August 10, 2006, doi:10.1165/rcmb.2006-0195OC Am. J. Respir. Cell Mol. Biol., Volume 36, Number 1, January 2007, 94-102 A more recent version of this article appeared on January 1, 2007
Submitted on June 2, 2006 SP-D Augments Bacterial Association but Attenuates MHC Class II Presentation of Bacterial AntigensSoren Hansen1,1 Department of Cell Biology, Duke University and Medical Center, Durham, NC, United States; The Medical Biotechnology Centre, University of Southern Denmark, Odense, Denmark, 2 Department of Cell Biology, Duke University and Medical Center, Durham, NC, United States, 3 Mendel Centre for Biomedical Sciences, Nicosia, Cyprus, 4 The Medical Biotechnology Centre, University of Southern Denmark, Odense, Denmark * To whom correspondence should be addressed. E-mail: j.wright{at}cellbio.duke.edu.
Surfactant protein D (SP-D) is a secreted pattern recognition molecule associated with lung surfactant and mediates in multiple ways the clearance of pathogens. SP-D is an established part of the innate immune system but it also modulates the adaptive immune response by interacting with both antigen-presenting cells and T-cells. In a previous work, antigen presentation by bone marrow derived dendritic cells was enhanced by SP-D. As dendritic cell function varies depending on their tissue of origin, we extended these studies to antigen-presenting cells isolated from mouse lung. Flow cytometric studies showed that SP-D binds calcium dependently and specifically to lung CD11c positive cells. Opsonization of fluorescently labeled E.coli by SP-D enhanced uptake by lung dendritic cells. SP-D facilitated the association of E.coli and antigen-presenting cells by increasing up to 10-fold the frequency of CD11+ cells associated with E.coli. In contrast to the effect on bone marrow derived dendritic cells, SP-D decreased the antigen presentation of ovalbumin, expressed in E.coli, to ovalbumin-specific MHC class II specific T-cell hybridomas by 30-50%. The reduction of antigen presentation did not depend on whether the dendritic cells were isolated from the lungs of non-stimulated mice or mice that had been exposed to LPS aerosols. Our results show that SP-D increases the opsonization of pathogens but decreases the antigen presentation by lung dendritic cells, and thereby potentially dampens the activation of T-cells and an adaptive immune response against bacterial antigens - during both steady state conditions and inflammation.
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