Cytokine Release in Healthy Donors and Patients with Chronic Granulomatous Disease upon Stimulation with Aspergillus fumigatus

2003 ◽  
Vol 35 (8) ◽  
pp. 482-487 ◽  
Author(s):  
Adilia Warris ◽  
Mihai G. Netea ◽  
Jacob E. Wang ◽  
Peter Gaustad ◽  
Bart-jan Kullberg ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Chronic Granulomatous Disease ◽  
Granulomatous Disease ◽  
Cytokine Release ◽  
Healthy Donors

scholarly journals Retroviral-Mediated Gene Transfer of gp91phox Into Bone Marrow Cells Rescues Defect in Host Defense Against Aspergillus fumigatus in Murine X-Linked Chronic Granulomatous Disease

Blood ◽  
1997 ◽  
Vol 89 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Helga Björgvinsdóttir ◽  
Chunjin Ding ◽  
Nancy Pech ◽  
Mary A. Gifford ◽  
Ling Lin Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Gene Transfer ◽  
Aspergillus Fumigatus ◽  
Chronic Granulomatous Disease ◽  
Host Defense ◽  
Bone Marrow Cells ◽  
Superoxide Production ◽  
Granulomatous Disease ◽  
Wild Type ◽  
Marrow Cells

Abstract The X-linked form of chronic granulomatous disease (X-CGD), an inherited deficiency of the respiratory burst oxidase, results from mutations in the X-linked gene for gp91phox, the larger subunit of the oxidase cytochrome b. The goal of this study was to evaluate the impact of retroviral-mediated gene transfer of gp91phox on host defense against Aspergillus fumigatus in a murine model of X-CGD. Retrovirus vectors constructed using the murine stem cell virus (MSCV) backbone were used for gene transfer of the gp91phox cDNA into murine X-CGD bone marrow cells. Transduced cells were transplanted into lethally irradiated syngeneic X-CGD mice. After hematologic recovery, superoxide production, as monitored by the nitroblue tetrazolium (NBT) test, was detected in up to ≈80% of peripheral blood neutrophils for at least 28 to 35 weeks after transplantation. Neutrophil expression of recombinant gp91phox and superoxide production were significantly less than wild-type neutrophils. However, 9 of 9 mice with ≈50% to 80% NBT+ neutrophils after gene transfer did not develop lung disease after respiratory challenge with 150 to 500 A fumigatus spores, doses that produced disease in 16 of 16 control X-CGD mice. In X-CGD mice transplanted with mixtures of wild-type and X-CGD bone marrow, ≥5% wild-type neutrophils were required for protection against A fumigatus challenge. These data suggest that expression of even low levels of recombinant gp91phox can substantially improve phagocyte function in X-CGD, although correction of very small percentage of phagocytes may not be sufficient for protection against A fumigatus.

scholarly journals Virulence and Cellular Interactions of Burkholderia multivorans in Chronic Granulomatous Disease

2009 ◽  
Vol 77 (10) ◽  
pp. 4337-4344 ◽  
Author(s):  
Adrian M. Zelazny ◽  
Li Ding ◽  
Houda Z. Elloumi ◽  
Lauren R. Brinster ◽  
Fran Benedetti ◽  
...  
Keyword(s):  
Chronic Granulomatous Disease ◽  
Burkholderia Cepacia ◽  
Cell Entry ◽  
Cellular Interactions ◽  
Granulomatous Disease ◽  
Burkholderia Multivorans ◽  
Healthy Donors ◽  
Cell Association ◽  
Life Threatening ◽  
Shed Light

ABSTRACT Chronic granulomatous disease (CGD) patients are susceptible to life-threatening infections by the Burkholderia cepacia complex. We used leukocytes from CGD and healthy donors and compared cell association, invasion, and cytokine induction by Burkholderia multivorans strains. A CGD isolate, CGD1, showed higher cell association than that of an environmental isolate, Env1, which correlated with cell entry. All B. multivorans strains associated significantly more with cells from CGD patients than with those from healthy donors. Similar findings were observed with another CGD pathogen, Serratia marcescens, but not with Escherichia coli. In a mouse model of CGD, strain CGD1 was virulent while Env1 was avirulent. B. multivorans organisms were found in the spleens of CGD1-infected mice at levels that were 1,000 times higher than those found in Env1-infected mice, which was coincident with higher levels of the proinflammatory cytokine interleukin-1β. Taken together, these results may shed light on the unique susceptibility of CGD patients to specific pathogens.

scholarly journals Enhanced Cutaneous Inflammatory Reactions to Aspergillus fumigatus in a Murine Model of Chronic Granulomatous Disease

2002 ◽  
Vol 118 (3) ◽  
pp. 424-429 ◽  
Author(s):  
Jeffrey E. Petersen ◽  
Tejindervir S. Hiran ◽  
W. Scott Goebel ◽  
Christopher Johnson ◽  
Robert C. Murphy ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Chronic Granulomatous Disease ◽  
Murine Model ◽  
Granulomatous Disease ◽  
Inflammatory Reactions

scholarly journals Chronic Granulomatous Disease Presenting as Aspergillus Fumigatus Pneumonia in a Previously Healthy Young Woman

2017 ◽  
Vol 18 ◽  
pp. 351-354 ◽  
Author(s):  
David Williams ◽  
Dipen Kadaria ◽  
Amik Sodhi ◽  
Roy Fox ◽  
Glenn Williams ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Chronic Granulomatous Disease ◽  
Young Woman ◽  
Granulomatous Disease ◽  
Healthy Young Woman

scholarly journals Retroviral-Mediated Gene Transfer of gp91phox Into Bone Marrow Cells Rescues Defect in Host Defense Against Aspergillus fumigatus in Murine X-Linked Chronic Granulomatous Disease

Blood ◽  
1997 ◽  
Vol 89 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Helga Björgvinsdóttir ◽  
Chunjin Ding ◽  
Nancy Pech ◽  
Mary A. Gifford ◽  
Ling Lin Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Gene Transfer ◽  
Aspergillus Fumigatus ◽  
Chronic Granulomatous Disease ◽  
Host Defense ◽  
Bone Marrow Cells ◽  
Superoxide Production ◽  
Granulomatous Disease ◽  
Wild Type ◽  
Marrow Cells

The X-linked form of chronic granulomatous disease (X-CGD), an inherited deficiency of the respiratory burst oxidase, results from mutations in the X-linked gene for gp91phox, the larger subunit of the oxidase cytochrome b. The goal of this study was to evaluate the impact of retroviral-mediated gene transfer of gp91phox on host defense against Aspergillus fumigatus in a murine model of X-CGD. Retrovirus vectors constructed using the murine stem cell virus (MSCV) backbone were used for gene transfer of the gp91phox cDNA into murine X-CGD bone marrow cells. Transduced cells were transplanted into lethally irradiated syngeneic X-CGD mice. After hematologic recovery, superoxide production, as monitored by the nitroblue tetrazolium (NBT) test, was detected in up to ≈80% of peripheral blood neutrophils for at least 28 to 35 weeks after transplantation. Neutrophil expression of recombinant gp91phox and superoxide production were significantly less than wild-type neutrophils. However, 9 of 9 mice with ≈50% to 80% NBT+ neutrophils after gene transfer did not develop lung disease after respiratory challenge with 150 to 500 A fumigatus spores, doses that produced disease in 16 of 16 control X-CGD mice. In X-CGD mice transplanted with mixtures of wild-type and X-CGD bone marrow, ≥5% wild-type neutrophils were required for protection against A fumigatus challenge. These data suggest that expression of even low levels of recombinant gp91phox can substantially improve phagocyte function in X-CGD, although correction of very small percentage of phagocytes may not be sufficient for protection against A fumigatus.

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