S. Florquin - Academia.edu (original) (raw)

Papers by S. Florquin

Journal of the American Society of Nephrology : JASN, Jan 23, 2015

Although both polyomavirus infection and T cell-mediated rejection (TCMR) are characterized by tu... more Although both polyomavirus infection and T cell-mediated rejection (TCMR) are characterized by tubulointerstitial inflammation in the renal allograft, these conditions are treated with opposing therapeutic regimens. To gain more insight into the differences between antiviral and alloimmune responses, we performed a case-control study, in which we immunophenotyped the inflammatory infiltrates in renal biopsy specimens with BK polyomavirus-associated nephropathy (BKPyVAN) and specimens with TCMR. Compared with TCMR, BKPyVAN was diagnosed later after transplantation; therefore, BKPyVAN specimens showed more chronic damage than TCMR specimens showed. However, TCMR and BKPyVAN specimens had comparable levels of tubulointerstitial inflammation. Adjustment for confounders in various multivariable models revealed more blood dendritic cell antigen-1(+) (BDCA-1(+)) myeloid dendritic cells (mDCs) present during BKPyVAN (odds ratio, 2.31; 95% confidence interval, 1.03 to 5.16; P=0.04) than duri...

Nephron Experimental Nephrology, 2005

t Background:: Tissue factor <TF) is a key i nitiator of the coagulation cascade. Recent evidence... more t Background:: Tissue factor <TF) is a key i nitiator of the coagulation cascade. Recent evidencee suggests that TF may play a role in renal fibrin formation and renal failuree in experimental kidney disease. We hypothesized that hyperglycemia willl result in increased expression of TF, which might play a role in the pathogenesiss of diabetic nephropathy.

Nephrology Dialysis Transplantation, 2007

The Journal of Immunology, 2003

The fatality rate associated with Streptococcus pneumoniae meningitis remains high despite adequa... more The fatality rate associated with Streptococcus pneumoniae meningitis remains high despite adequate antibiotic treatment. IL-1 is an important proinflammatory cytokine, which is up-regulated in brain tissue after the induction of meningitis. To determine the role of IL-1 in pneumococcal meningitis we induced meningitis by intranasal inoculation with 8 ؋ 10 4 CFU of S. pneumoniae and 180 U of hyaluronidase in IL-1R type I gene-deficient (IL-1R ؊/؊ ) mice and wild-type mice. Meningitis resulted in elevated IL-1␣ and IL-1␤ mRNA and protein levels in the brain. The absence of an intact IL-1 signal was associated with a higher susceptibility to develop meningitis. Furthermore, the lack of IL-1 impaired bacterial clearance, as reflected by an increased number of CFU in cerebrospinal fluid of IL-1R ؊/؊ mice. The characteristic pleocytosis of meningitis was not significantly altered in IL-1R ؊/؊ mice, but meningitis was associated with lower brain levels of cytokines. The mortality was significantly higher and earlier in the course of the disease in IL-1R ؊/؊ mice. These results demonstrate that endogenous IL-1 is required for an adequate host defense in pneumococcal meningitis.

Infection and Immunity, 2007

Melioidosis is caused by the soil saprophyte Burkholderia pseudomallei and is endemic in Southeas... more Melioidosis is caused by the soil saprophyte Burkholderia pseudomallei and is endemic in Southeast Asia. The pathogenesis of melioidosis is still largely unknown, although gamma interferon (IFN-␥) seems to play an obligatory role in host defense. Previously, we have shown that IFN-␥ production in melioidosis is controlled in part by interleukin-18 (IL-18). The aim of the present study was to determine the role of IL-18 in the immune response to B. pseudomallei. For this the following investigations were performed. (i) Plasma IL-18 and blood monocyte IL-18 mRNA levels were elevated in 34 patients with culture-proven melioidosis compared to the levels in 32 local healthy controls; in addition, IL-18 binding protein levels were markedly elevated in patients, strongly correlating with mortality. (ii) IL-18 gene-deficient (IL-18 knockout [KO]) mice showed accelerated mortality after intranasal infection with a lethal dose of B. pseudomallei, which was accompanied by enhanced bacterial growth in their lungs, livers, spleens, kidneys, and blood at 24 and 48 h postinfection, compared to wild-type mice. In addition, IL-18 KO mice displayed evidence of enhanced hepatocellular injury and renal insufficiency. Together, these data indicate that the enhanced production of IL-18 in melioidosis is an essential part of a protective immune response to this severe infection.

Critical Care Medicine, 2006

The tissue factor (TF)-factor VIIa (FVIIa) complex not only is essential for activation of blood ... more The tissue factor (TF)-factor VIIa (FVIIa) complex not only is essential for activation of blood coagulation but also affect the inflammatory response during sepsis. The objective of this study was to determine the role of TF-FVIIa in pneumonia caused by Streptococcus pneumoniae, the most important causative organism in community-acquired pneumonia and a major cause of sepsis. A controlled, in vivo laboratory study. Research laboratory of a health sciences university. Patients with unilateral community-acquired pneumonia and female BALB/c mice. Bilateral bronchoalveolar lavage was performed in patients with community-acquired pneumonia. In mice, pneumonia was induced by intranasal inoculation with S. pneumoniae with or without concurrent inhibition of TF-FVIIa by subcutaneous injections of recombinant nematode anticoagulant protein (rNAPc2). Patients with unilateral community-acquired pneumonia demonstrated elevated concentrations of FVIIa, soluble TF, and thrombin-antithrombin complexes in bronchoalveolar lavage fluid obtained from the infected site compared with the uninfected site. Mice with S. pneumoniae pneumonia displayed increased TF expression and fibrin deposits in lungs together with elevated thrombin-antithrombin complex levels in bronchoalveolar lavage fluid; inhibition of TF-FVIIa by rNAPc2 attenuated the procoagulant response in the lung but did not affect host defense, as reflected by an unaltered outgrowth of pneumococci and an unchanged survival. These data suggest that TF-FVIIa activity contributes to activation of coagulation in the lung during pneumococcal pneumonia but does not play an important role in the antibacterial host defense in this murine model.

Clinical and Experimental Immunology, 2002

Blood Cells, Molecules, and Diseases, 2004

During endotoxemia, blood coagulation becomes activated due to tissue factor (TF) expression on l... more During endotoxemia, blood coagulation becomes activated due to tissue factor (TF) expression on leukocytes and/or endothelial cells. We investigated the influence of blood cell-derived tissue factor on murine endotoxemia. Therefore, we generated mice that lack tissue factor on their blood cells by transplanting tissue factor-deficient hematopoietic stem cells into lethally irradiated wild-type recipients. Control mice were also irradiated but were injected with stem cells from wild-type littermate embryos. Seven weeks after transplantation, the mice received 250 microg of endotoxin intraperitoneally. Three hours later, the mice were bled and plasma and organs were collected to assess inflammation, coagulation, and apoptosis. Mice that lack tissue factor on their blood cells still reacted to endotoxemia, but markedly less than wild-type controls. Blood cell-derived tissue factor-deficient mice showed significantly less clinical symptoms than control mice. Levels of circulating inflammatory mediators and thrombin-antithrombin (TAT) complexes were lower in blood cell-derived tissue factor-deficient mice than in controls. Surprisingly, inflammation was seen more often in blood cell-derived tissue factor-deficient mice than in control mice, but signs of apoptosis were more pronounced in controls. In summary, our data clearly indicate that endotoxin-induced coagulation and inflammation are strongly influenced by blood cell-derived tissue factor.

Journal of Leukocyte Biology, 2008

Overexpression of CD95 (Fas/Apo-1) ligand (CD95L) has been shown to induce T cell tolerance but a... more Overexpression of CD95 (Fas/Apo-1) ligand (CD95L) has been shown to induce T cell tolerance but also, neutrophilic inflammation and rejection of allogeneic tissue. We explored the capacity of dendritic cells (DCs) genetically engineered to overexpress CD95L to induce an antitumor response. We first found that DCs overexpressing CD95L, in addition to MHC class I-restricted OVA peptides (CD95L-OVA-DCs), induced increased antigen-specific CD8 ؉ T cell responses as compared with DCs overexpressing OVA peptides alone. The enhanced T cell responses were associated with improved regression of a tumor expressing OVA, allowing survival of all animals. When DCs overexpressing CD95L (CD95L-DCs) were injected with the tumor expressing OVA, in vivo tumor proliferation was strikingly inhibited. A strong cellular apoptosis and a massive neutrophilic infiltrate developed in this setting. Neutrophil depletion prevented tumor regression as well as enhanced IFN-␥ production induced by CD95L-OVA-DCs. Furthermore, the CD8 ؉ T cell response induced by the coadministration of tumor cells and CD95L-DCs led to rejection of a tumor implanted at a distance from the DC injection site. In summary, DCs expressing CD95L promote tumor rejection involving neutrophil-mediated innate immunity and CD8 ؉ T celldependent adaptative immune responses. J. Leukoc. Biol. 84: 000 -000; 2008.