|
|
||||||||
CUTTING EDGE |

*
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520; and
Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
The agent of human granulocytic ehrlichiosis (HGE) is an emerging tick-borne pathogen that resides in neutrophils and can be cultured in a promyelocytic (HL-60) cell line. In response to microbes, polymorphonuclear leukocytes normally activate the NADPH oxidase enzyme complex and generate superoxide anion (O2-). However, HL-60 cells infected with HGE bacteria did not produce O2- upon activation with PMA. RT-PCR demonstrated that HGE organisms inhibited mRNA expression of a single component of NADPH oxidase, gp91phox, and FACS analysis showed that plasma membrane-associated gp91phox protein was reduced on the infected cells. Infection with HGE organisms also decreased gp91phox mRNA levels in splenic neutrophils in a murine model of HGE, demonstrating this phenomenon in vivo. Therefore, HGE bacteria repress the respiratory burst by down-regulating gp91phox, the first direct inhibition of NADPH oxidase by a pathogen.
This article has been cited by other articles:
![]() |
V. Thomas, S. Samanta, and E. Fikrig Anaplasma phagocytophilum Increases Cathepsin L Activity, Thereby Globally Influencing Neutrophil Function Infect. Immun., November 1, 2008; 76(11): 4905 - 4912. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. G. Scorpio, F. D. von Loewenich, H. Gobel, C. Bogdan, and J. S. Dumler Innate Immune Response to Anaplasma phagocytophilum Contributes to Hepatic Injury. Clin. Vaccine Immunol., July 1, 2006; 13(7): 806 - 809. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Yager, C. Bitsaktsis, B. Nandi, J. W. McBride, and G. Winslow Essential Role for Humoral Immunity during Ehrlichia Infection in Immunocompetent Mice Infect. Immun., December 1, 2005; 73(12): 8009 - 8016. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Sukumaran, J. A. Carlyon, J.-L. Cai, N. Berliner, and E. Fikrig Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection Infect. Immun., December 1, 2005; 73(12): 8089 - 8099. [Abstract] [Full Text] [PDF] |
||||
![]() |
N.-K. Pham, J. Mouriz, and P. E. Kima Leishmania pifanoi Amastigotes Avoid Macrophage Production of Superoxide by Inducing Heme Degradation Infect. Immun., December 1, 2005; 73(12): 8322 - 8333. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Carlyon, D. Ryan, K. Archer, and E. Fikrig Effects of Anaplasma phagocytophilum on Host Cell Ferritin mRNA and Protein Levels Infect. Immun., November 1, 2005; 73(11): 7629 - 7636. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. R. Abbott, G. H. Palmer, K. A. Kegerreis, P. F. Hetrick, C. J. Howard, J. C. Hope, and W. C. Brown Rapid and Long-Term Disappearance of CD4+ T Lymphocyte Responses Specific for Anaplasma Marginale Major Surface Protein-2 (MSP2) in MSP2 Vaccinates following Challenge with Live A. marginale J. Immunol., June 1, 2005; 174(11): 6702 - 6715. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. L. Borjesson, S. D. Kobayashi, A. R. Whitney, J. M. Voyich, C. M. Argue, and F. R. DeLeo Insights into Pathogen Immune Evasion Mechanisms: Anaplasma phagocytophilum Fails to Induce an Apoptosis Differentiation Program in Human Neutrophils J. Immunol., May 15, 2005; 174(10): 6364 - 6372. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. W. A. Garyu, K.-s. Choi, D. J. Grab, and J. S. Dumler Defective Phagocytosis in Anaplasma phagocytophilum- Infected Neutrophils Infect. Immun., February 1, 2005; 73(2): 1187 - 1190. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Thomas, S. Samanta, C. Wu, N. Berliner, and E. Fikrig Anaplasma phagocytophilum Modulates gp91phox Gene Expression through Altered Interferon Regulatory Factor 1 and PU.1 Levels and Binding of CCAAT Displacement Protein Infect. Immun., January 1, 2005; 73(1): 208 - 218. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. W. IJdo and A. C. Mueller Neutrophil NADPH Oxidase Is Reduced at the Anaplasma phagocytophilum Phagosome Infect. Immun., September 1, 2004; 72(9): 5392 - 5401. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Carlyon, D. A. Latif, M. Pypaert, P. Lacy, and E. Fikrig Anaplasma phagocytophilum Utilizes Multiple Host Evasion Mechanisms To Thwart NADPH Oxidase-Mediated Killing during Neutrophil Infection Infect. Immun., August 1, 2004; 72(8): 4772 - 4783. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Tsunawaki, L. S. Yoshida, S. Nishida, T. Kobayashi, and T. Shimoyama Fungal Metabolite Gliotoxin Inhibits Assembly of the Human Respiratory Burst NADPH Oxidase Infect. Immun., June 1, 2004; 72(6): 3373 - 3382. [Abstract] [Full Text] [PDF] |
||||
![]() |
K.-s. Choi, D. J. Grab, and J. S. Dumler Anaplasma phagocytophilum Infection Induces Protracted Neutrophil Degranulation Infect. Immun., June 1, 2004; 72(6): 3680 - 3683. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Park, K.-S. Choi, D. J. Grab, and J. S. Dumler Divergent Interactions of Ehrlichia chaffeensis- and Anaplasma phagocytophilum-Infected Leukocytes with Endothelial Cell Barriers Infect. Immun., December 1, 2003; 71(12): 6728 - 6733. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Carlyon, M. Akkoyunlu, L. Xia, T. Yago, T. Wang, R. D. Cummings, R. P. McEver, and E. Fikrig Murine neutrophils require {alpha}1,3-fucosylation but not PSGL-1 for productive infection with Anaplasma phagocytophilum Blood, November 1, 2003; 102(9): 3387 - 3395. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Lin and Y. Rikihisa Ehrlichia chaffeensis and Anaplasma phagocytophilum Lack Genes for Lipid A Biosynthesis and Incorporate Cholesterol for Their Survival Infect. Immun., September 1, 2003; 71(9): 5324 - 5331. [Abstract] [Full Text] [PDF] |
||||
![]() |
K.-S. Choi, J. Garyu, J. Park, and J. S. Dumler Diminished Adhesion of Anaplasma phagocytophilum-Infected Neutrophils to Endothelial Cells Is Associated with Reduced Expression of Leukocyte Surface Selectin Infect. Immun., August 1, 2003; 71(8): 4586 - 4594. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Scaife, Z. Woldehiwet, C. A. Hart, and S. W. Edwards Anaplasma phagocytophilum Reduces Neutrophil Apoptosis In Vivo Infect. Immun., April 1, 2003; 71(4): 1995 - 2001. [Abstract] [Full Text] |
||||
![]() |
J. A. Carlyon, W.-T. Chan, J. Galan, D. Roos, and E. Fikrig Repression of rac2 mRNA Expression by Anaplasma phagocytophila Is Essential to the Inhibition of Superoxide Production and Bacterial Proliferation J. Immunol., December 15, 2002; 169(12): 7009 - 7018. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. W. IJdo, C. Wu, S. R. Telford III, and E. Fikrig Differential Expression of the p44 Gene Family in the Agent of Human Granulocytic Ehrlichiosis Infect. Immun., September 1, 2002; 70(9): 5295 - 5298. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Mott, Y. Rikihisa, and S. Tsunawaki Effects of Anaplasma phagocytophila on NADPH Oxidase Components in Human Neutrophils and HL-60 Cells Infect. Immun., March 1, 2002; 70(3): 1359 - 1366. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. R. Ganta, M. J. Wilkerson, C. Cheng, A. M. Rokey, and S. K. Chapes Persistent Ehrlichia chaffeensis Infection Occurs in the Absence of Functional Major Histocompatibility Complex Class II Genes Infect. Immun., January 1, 2002; 70(1): 380 - 388. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Akkoyunlu, S. E. Malawista, J. Anguita, and E. Fikrig Exploitation of Interleukin-8-Induced Neutrophil Chemotaxis by the Agent of Human Granulocytic Ehrlichiosis Infect. Immun., September 1, 2001; 69(9): 5577 - 5588. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Mott and Y. Rikihisa Human Granulocytic Ehrlichiosis Agent Inhibits Superoxide Anion Generation by Human Neutrophils Infect. Immun., December 1, 2000; 68(12): 6697 - 6703. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Banerjee, J. Anguita, and E. Fikrig Granulocytic Ehrlichiosis in Mice Deficient in Phagocyte Oxidase or Inducible Nitric Oxide Synthase Infect. Immun., July 1, 2000; 68(7): 4361 - 4362. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |