Epidémie d'infections du site opératoire à Serratia marcescens associée à l'utilisation d'une sonde d'échographie

International audienc

Neutrophils: the forgotten cell in JIA disease pathogenesis

Juvenile idiopathic arthritis (JIA) has long been assumed to be an autoimmune disease, triggered by aberrant recognition of "self" antigens by T-cells. However, systems biology approaches to this family of diseases have suggested complex interactions between innate and adaptive immunity that underlie JIA. In particular, new data suggest an important role for neutrophils in JIA pathogenesis. In this short review, we will discuss the new data that support a role for neutrophils in JIA, discuss regulatory functions that link neutrophils to adaptive immune responses, and discuss future areas of investigation. Above all else, we invite the reader to re-consider the use of the term "autoimmunity" as applied to the family of illnesses we collectively call JIA

Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice

Background Recent in vivo and in vitro studies in non-neuronal and neuronal tissues have shown that different pathways of macrophage activation result in cells with different properties. Interleukin (IL)-6 triggers the classically activated inflammatory macrophages (M1 phenotype), whereas the alternatively activated macrophages (M2 phenotype) are anti-inflammatory. The objective of this study was to clarify the effects of a temporal blockade of IL-6/IL-6 receptor (IL-6R) engagement, using an anti-mouse IL-6R monoclonal antibody (MR16-1), on macrophage activation and the inflammatory response in the acute phase after spinal cord injury (SCI) in mice. Methods MR16-1 antibodies versus isotype control antibodies or saline alone were administered immediately after thoracic SCI in mice. SC tissue repair was compared between the two groups by Luxol fast blue (LFB) staining for myelination and immunoreactivity for the neuronal markers growth-associated protein (GAP)-43 and neurofilament heavy 200 kDa (NF-H) and for locomotor function. The expression of T helper (Th)1 cytokines (interferon (IFN)-? and tumor necrosis factor-a) and Th2 cytokines (IL-4, IL-13) was determined by immunoblot analysis. The presence of M1 (inducible nitric oxide synthase (iNOS)-positive, CD16/32-positive) and M2 (arginase 1-positive, CD206-positive) macrophages was determined by immunohistology. Using flow cytometry, we also quantified IFN-? and IL-4 levels in neutrophils, microglia, and macrophages, and Mac-2 (macrophage antigen-2) and Mac-3 in M2 macrophages and microglia. Results LFB-positive spared myelin was increased in the MR16-1-treated group compared with the controls, and this increase correlated with enhanced positivity for GAP-43 or NF-H, and improved locomotor Basso Mouse Scale scores. Immunoblot analysis of the MR16-1-treated samples identified downregulation of Th1 and upregulation of Th2 cytokines. Whereas iNOS-positive, CD16/32-positive M1 macrophages were the predominant phenotype in the injured SC of non-treated control mice, MR16-1 treatment promoted arginase 1-positive, CD206-positive M2 macrophages, with preferential localization of these cells at the injury site. MR16-1 treatment suppressed the number of IFN-?-positive neutrophils, and increased the number of microglia present and their positivity for IL-4. Among the arginase 1-positive M2 macrophages, MR16-1 treatment increased positivity for Mac-2 and Mac-3, suggestive of increased phagocytic behavior. Conclusion The results suggest that temporal blockade of IL-6 signaling after SCI abrogates damaging inflammatory activity and promotes functional recovery by promoting the formation of alternatively activated M2 macrophages

In vivo selection of multidrug resistance in Enterobacter cloacae complex by a unique romR deletion

International audienceObjectives: Members of the Enterobacter cloacae complex (ECC) are major opportunistic pathogens, especially among intensive care unit (ICU) patients. The aim of this study was to decipher the phenotypic and genomic evolution of an ECC clone that acquired a multidrug resistance phenotype in an ICU patient. Methods: During a four-month period, 8 MDR ECC strains were recovered from the same patient: 5 from clinical samples and 3 from rectal swabs. The patient benefited from an escalation of antibiotic treatment until he died. MIC values of 18 antibiotics were determined by the broth microdilution method. Whole-genome sequencing was performed for the 8 strains and a Single-Nucleotide Polymorphism (SNP) analysis was performed after alignment against the ECC reference genome (ATCC 13047). Results: In strains isolated from the 3rd month, a significant increase in MICs (at least 4 fold change) was observed for ceftazidime, cefepime, temocillin, ertapenem, tigecycline and chloramphenicol. All strains harbored the same antibiotic resistance genes against β-lactams, aminoglycosides, fluoroquinolones, sulphonamides, trimethoprime and chloramphenicol. The 8 MDR ECC belonged to the same cluster 6 (ECC6) and were genetically related. No genetic evolution was found in chromosomal genes usually involved in β-lactam resistance (i.e. ampD, ampR, nagZ, dacA, dacB, acrAB-tolC, ompK35, ompK36). The isolates differed by 5 SNPs located in metabolism genes and a deletion of 13 bases in romR, which encodes for TetR-type transcriptonal regulator. This latter is known to play a repressor role on the expression of porins such as ompK35, whose the downregulation might be involved in MIC increases observed here. Conclusion: Consequent and long-term antibiotic treatment in one patient indicated the selection of a unique MDR ECC6 population where antibiotic resistance evolved more by chromosomal modifications than acquired antibiotic resistance genes. The analysis of the different genetic features through all the 8 MDR ECC6 strains allowed us to highlight a candidate gene that could be implicated in carbapenem, chloramphenicol and tigecyclin resistance. Further phenotypic and molecular characterization by site-directed mutagenesis is in progress

In vivo selection of multidrug resistance in Enterobacter cloacae complex by a unique romR deletion

International audienceObjectives: Members of the Enterobacter cloacae complex (ECC) are major opportunistic pathogens, especially among intensive care unit (ICU) patients. The aim of this study was to decipher the phenotypic and genomic evolution of an ECC clone that acquired a multidrug resistance phenotype in an ICU patient. Methods: During a four-month period, 8 MDR ECC strains were recovered from the same patient: 5 from clinical samples and 3 from rectal swabs. The patient benefited from an escalation of antibiotic treatment until he died. MIC values of 18 antibiotics were determined by the broth microdilution method. Whole-genome sequencing was performed for the 8 strains and a Single-Nucleotide Polymorphism (SNP) analysis was performed after alignment against the ECC reference genome (ATCC 13047). Results: In strains isolated from the 3rd month, a significant increase in MICs (at least 4 fold change) was observed for ceftazidime, cefepime, temocillin, ertapenem, tigecycline and chloramphenicol. All strains harbored the same antibiotic resistance genes against β-lactams, aminoglycosides, fluoroquinolones, sulphonamides, trimethoprime and chloramphenicol. The 8 MDR ECC belonged to the same cluster 6 (ECC6) and were genetically related. No genetic evolution was found in chromosomal genes usually involved in β-lactam resistance (i.e. ampD, ampR, nagZ, dacA, dacB, acrAB-tolC, ompK35, ompK36). The isolates differed by 5 SNPs located in metabolism genes and a deletion of 13 bases in romR, which encodes for TetR-type transcriptonal regulator. This latter is known to play a repressor role on the expression of porins such as ompK35, whose the downregulation might be involved in MIC increases observed here. Conclusion: Consequent and long-term antibiotic treatment in one patient indicated the selection of a unique MDR ECC6 population where antibiotic resistance evolved more by chromosomal modifications than acquired antibiotic resistance genes. The analysis of the different genetic features through all the 8 MDR ECC6 strains allowed us to highlight a candidate gene that could be implicated in carbapenem, chloramphenicol and tigecyclin resistance. Further phenotypic and molecular characterization by site-directed mutagenesis is in progress

Investigation of Serratia marcescens surgical site infection outbreak associated with peroperative ultrasonography probe

International audienc

Epidémie d'infections du site opératoire à Serratia marcescens associée à l'utilisation d'une sonde d'échographie

International audienc

Résistance aux biocides des souches Pseudomonas productrices de carbapènémases de type VIM-2 : impact sur les détergents-désinfectants usuels

National audienc