Hydrodynamic regulation of monocyte inflammatory response to an intracellular pathogen.
Systemic bacterial infections elicit inflammatory response that promotes acute or chronic complications such as sepsis, arthritis or atherosclerosis. Of interest, cells in circulation experience hydrodynamic shear forces, which have been shown to be a potent regulator of cellular function in the vasculature and play an important role in maintaining tissue homeostasis. In this study, we have examined the effect of shear forces due to blood flow in modulating the inflammatory response of cells to infection. Using an in vitro model, we analyzed the effects of physiological levels of shear stress on the inflammatory response of monocytes infected with chlamydia, an intracellular pathogen which causes bronchitis and is implicated in the development of atherosclerosis. We found that chlamydial infection alters the morphology of monocytes and trigger the release of pro-inflammatory cytokines TNF-α, IL-8, IL-1β and IL-6. We also found that the exposure of chlamydia-infected monocytes to short durations of arterial shear stress significantly enhances the secretion of cytokines in a time-dependent manner and the expression of surface adhesion molecule ICAM-1. As a functional consequence, infection and shear stress increased monocyte adhesion to endothelial cells under flow and in the activation and aggregation of platelets. Overall, our study demonstrates that shear stress enhances the inflammatory response of monocytes to infection, suggesting that mechanical forces may contribute to disease pathophysiology. These results provide a novel perspective on our understanding of systemic infection and inflammation.
Department of Biomedical Engineering, The University of Texas at San Antonio, San Antonio, Texas, United States of America.
Shankar J
SJ
Evani
Ashlesh K
AK
Murthy
Naresh
N
Mareedu
Robbie K
RK
Montgomery
Bernard P
BP
Arulanandam
Anand K
AK
Ramasubramanian
D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000276:immunology; D049674:History, 21st Century; D007249:Inflammation; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000382:microbiology*
Cardiol Clin. 2003 Aug;21(3):333-62
14621450
Clin Vaccine Immunol. 2007 Dec;14(12):1537-44
17942608
Experientia. 1991 Jan 15;47(1):22-31
1999239
J Infect Dis. 2003 Nov 1;188(9):1310-21
14593587
J Immunol. 2007 Jan 15;178(2):1048-58
17202368
Blood. 1996 Sep 1;88(5):1525-41
8781407
Biorheology. 2001;38(2-3):185-201
11381174
Clin Exp Immunol. 2000 Sep;121(3):437-43
10971508
Endothelium. 1998;6(1):33-44
9832331
Physiol Rev. 2006 Apr;86(2):515-81
16601268
Eur Respir J. 2004 Apr;23(4):506-10
15083745
Antimicrob Agents Chemother. 2009 Nov;53(11):4604-11
19687238
Nature. 1999 Apr 22;398(6729):718-23
10227295
Microbiol Rev. 1994 Dec;58(4):686-99
7854252
Nat Rev Microbiol. 2004 Jan;2(1):23-32
15035006
Annu Rev Med. 2008;59:415-28
17937586
Eur J Immunol. 2000 Feb;30(2):541-9
10671210
J Immunol. 2004 Jul 15;173(2):1258-65
15240718
Clin Sci (Lond). 2008 Apr;114(8):509-31
18336368
Nat Med. 2003 Jan;9(1):61-7
12483207
Circulation. 1999 Sep 28;100(13):1369-73
10500035
J Cell Sci. 2003 Apr 1;116(Pt 7):1157-73
12615960
Vaccine. 2006 Jan 16;24(3):355-66
16153755
Nat Rev Mol Cell Biol. 2009 Jan;10(1):53-62
19197332
Microbes Infect. 2006 Feb;8(2):478-86
16297651
J Immunol. 2008 Feb 15;180(4):2225-32
18250429
Microbes Infect. 2010 Aug;12(8-9):598-606
20417302
Cell Microbiol. 2006 Jun;8(6):1047-57
16681844
N Engl J Med. 1999 Jan 14;340(2):115-26
9887164
N Engl J Med. 2007 Dec 13;357(24):2482-94
18077812
Int J Med Microbiol. 2007 Apr;297(2):109-15
17280867
J Immunol. 2008 Aug 1;181(3):2092-102
18641348
Biorheology. 2006;43(5):681-91
17047284
Infect Immun. 2007 Aug;75(8):3707-14
17502393
Cell Host Microbe. 2008 Aug 14;4(2):159-69
18692775
Arterioscler Thromb Vasc Biol. 2003 Dec;23(12):2131-7
14500287
Lab Invest. 2005 Jan;85(1):9-23
15568038
Blood. 2010 Mar 18;115(11):2274-82
19996090
Nat Rev Microbiol. 2006 Jun;4(6):445-57
16710325
Nat Rev Immunol. 2007 Sep;7(9):678-89
17717539
Cardiovasc Res. 2003 Oct 15;60(1):26-39
14522404
Clin Microbiol Rev. 1995 Oct;8(4):451-61
8665464
Ann N Y Acad Sci. 1998 Sep 29;856:1-11
9917859
J Immunol. 2008 Jan 15;180(2):1158-68
18178856