Surfactant protein-A inhibits mycoplasma-induced dendritic cell maturation through regulation of HMGB-1 cytokine activity.
During pulmonary infections, a careful balance between activation of protective host defense mechanisms and potentially injurious inflammatory processes must be maintained. Surfactant protein A (SP-A) is an immune modulator that increases pathogen uptake and clearance by phagocytes while minimizing lung inflammation by limiting dendritic cell (DC) and T cell activation. Recent publications have shown that SP-A binds to and is bacteriostatic for Mycoplasma pneumoniae in vitro. In vivo, SP-A aids in maintenance of airway homeostasis during M. pneumoniae pulmonary infection by preventing an overzealous proinflammatory response mediated by TNF-α. Although SP-A was shown to inhibit maturation of DCs in vitro, the consequence of DC/SP-A interactions in vivo has not been elucidated. In this article, we show that the absence of SP-A during M. pneumoniae infection leads to increased numbers of mature DCs in the lung and draining lymph nodes during the acute phase of infection and, consequently, increased numbers of activated T and B cells during the course of infection. The findings that glycyrrhizin, a specific inhibitor of extracellular high-mobility group box-1 (HMGB-1) abrogated this effect and that SP-A inhibits HMGB-1 release from immune cells suggest that SP-A inhibits M. pneumoniae-induced DC maturation by regulating HMGB-1 cytokine activity.
Ledford
Julie G
JG
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Lo
Bernice
B
Kislan
Michele M
MM
Thomas
Joseph M
JM
Evans
Katherine
K
Cain
Derek W
DW
Kraft
Monica
M
Williams
Kristi L
KL
Wright
Jo Rae
JR
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D024243:HMGB1 Protein / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009175:Mycoplasma Infections / Q000276:immunology* / Q000378:metabolism; D009177:Mycoplasma pneumoniae / Q000276:immunology; D037662:Pulmonary Surfactant-Associated Protein A / Q000276:immunology* / Q000378:metabolism
D024243:HMGB1 Protein; D037662:Pulmonary Surfactant-Associated Protein A
J Allergy Clin Immunol. 2001 Apr;107(4):595-601
11295645
Arerugi. 1991 Jan;40(1):21-7
2029217
J Immunol. 2005 Jun 15;174(12):7506-15
15944249
Infect Immun. 1995 Oct;63(10):4138-42
7558330
J Infect Dis. 2006 Jan 15;193(2):205-13
16362884
J Leukoc Biol. 2007 Jan;81(1):100-7
16935945
Proc Am Thorac Soc. 2007 Jul;4(3):234-9
17607005
Am J Physiol. 1996 Aug;271(2 Pt 1):L310-9
8770070
Int Immunol. 2006 Nov;18(11):1563-73
16966494
Nat Rev Immunol. 2005 Jan;5(1):58-68
15630429
Rheumatology (Oxford). 2009 Oct;48(10):1190-6
19589888
Eur J Immunol. 2005 Jul;35(7):2184-90
15915542
J Exp Med. 2000 Aug 21;192(4):565-70
10952726
J Exp Med. 1992 Dec 1;176(6):1693-702
1460426
J Immunol. 2008 Feb 15;180(4):2562-72
18250467
Chem Biol. 2007 Apr;14(4):345-7
17462568
J Biol Chem. 2005 Jan 7;280(1):9-17
15498759
J Asthma. 2009 Apr;46(3):265-9
19373634
Am J Physiol Lung Cell Mol Physiol. 2001 Dec;281(6):L1453-63
11704542
Blood. 2003 Sep 15;102(6):2187-94
12791652
Infect Immun. 2005 May;73(5):2828-34
15845487
Am J Physiol. 1998 Oct;275(4):L679-86
9755099
J Immunol. 2009 Jun 15;182(12):7818-27
19494306
J Immunol. 1995 Oct 1;155(7):3292-5
7561021
Cell Immunol. 2009;254(2):94-104
18762288
J Exp Med. 1996 Dec 1;184(6):2429-32
8976199
Eur J Immunol. 2004 Jun;34(6):1503-12
15162419
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9594-9
8790375
Clin Microbiol Rev. 2004 Oct;17(4):697-728, table of contents
15489344
Am J Physiol Lung Cell Mol Physiol. 2003 Jan;284(1):L232-41
12388334
J Exp Med. 2001 Jan 1;193(1):51-60
11136820
Chem Biol. 2007 Apr;14(4):431-41
17462578
EMBO J. 2003 Oct 15;22(20):5551-60
14532127
Am J Respir Crit Care Med. 1998 Sep;158(3):998-1001
9731038
Eur Respir J. 2001 Oct;18(4):692-704
11716176