Efficacy of daptomycin in implant-associated infection due to methicillin-resistant Staphylococcus aureus: importance of combination with rifampin.

Limited treatment options are available for implant-associated infections caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). We compared the activity of daptomycin (alone and with rifampin [rifampicin]) with the activities of other antimicrobial regimens against MRSA ATCC 43300 in the guinea pig foreign-body infection model. The daptomycin MIC and the minimum bactericidal concentration in logarithmic phase and stationary growth phase of MRSA were 0.

Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues.

Constitutive egress of bone marrow (BM)-resident hematopoietic stem and progenitor cells (HSPCs) into the blood is a well-established phenomenon, but the ultimate fate and functional relevance of circulating HSPCs is largely unknown. We show that mouse thoracic duct (TD) lymph contains HSPCs that possess short- and long-term multilineage reconstitution capacity. TD-derived HSPCs originate in the BM, enter the blood, and traffic to multiple peripheral organs, where they reside for at least 36 hr before entering draining lymphatics to return to the blood and, eventually, the BM.

Initiation of protein O glycosylation by the polypeptide GalNAcT-1 in vascular biology and humoral immunity.

Core-type protein O glycosylation is initiated by polypeptide N-acetylgalactosamine (GalNAc) transferase (ppGalNAcT) activity and produces the covalent linkage of serine and threonine residues of proteins. More than a dozen ppGalNAcTs operate within multicellular organisms, and they differ with respect to expression patterns and substrate selectivity. These distinctive features imply that each ppGalNAcT may differentially modulate regulatory processes in animal development, physiology, and perhaps disease.

Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment.

Lymphocyte homing is mediated by specific interaction between L-selectin on lymphocytes and the carbohydrate ligand 6-sulfo sialyl Lewis X on high endothelial venules. Here we generated mice lacking both core 1 extension and core 2 branching enzymes to assess the functions of O-glycan-borne L-selectin ligands in vivo. Mutant mice maintained robust lymphocyte homing, yet they lacked O-glycan L-selectin ligands.

Murine CXCL14 is dispensable for dendritic cell function and localization within peripheral tissues.

Dendritic cells (DCs) have long been recognized as key regulators of immune responses. However, the process of their recruitment to peripheral tissues and turnover during homeostasis remains largely unknown. The chemokine CXCL14 (BRAK) is constitutively expressed in skin and other epithelial tissues.

Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus.

Dendritic cell (DC) presentation of self antigen to thymocytes is essential to the establishment of central tolerance. We show here that circulating DCs were recruited to the thymic medulla through a three-step adhesion cascade involving P-selectin, interactions of the integrin VLA-4 with its ligand VCAM-1, and pertussis toxin-sensitive chemoattractant signaling. Ovalbumin-specific OT-II thymocytes were selectively deleted after intravenous injection of antigen-loaded exogenous DCs.

Compartment-specific expression and function of the chemokine IP-10/CXCL10 in a model of renal endothelial microvascular injury.

The recruitment of inflammatory cells into renal tissue, mainly T cells and monocytes, is a typical feature of various renal diseases such as glomerulonephritis, thrombotic angiopathies, allograft rejection, and vasculitis. T cells predominantly infiltrate the tubulointerstitium, whereas monocytes are present in the tubulointerstitial and glomerular compartment. Because chemokines play a pivotal role in leukocyte trafficking under inflammatory conditions, this study investigated whether a differential expression of chemokines contributes to the precise coordination of leukocyte subtype trafficking in a rat model of renal microvascular endothelial injury.

T cell-regulated neutrophilic inflammation in autoinflammatory diseases.

Previous studies of acute generalized exanthematous pustulosis, a peculiar drug hypersensitivity reaction, suggested that CXCL8-producing T cells regulate sterile, polymorphonuclear neutrophil-rich skin inflammations. In this study, we test the hypothesis of whether CXCL8-producing T cells are present in autoinflammatory diseases like pustular psoriasis and Behçet's disease. Immunohistochemistry of normal skin revealed few CD4+ and CD8+ T cells, few CXCL8+ cells, and no neutrophilic infiltration, whereas in acute exacerbations of atopic dermatitis, numerous CD4+ T cells but few CD8+ T cells, neutrophils, or CXCL8+ cells were detected.

Cutaneous CXCL14 targets blood precursors to epidermal niches for Langerhans cell differentiation.

Dendritic cells (DCs) are major constituents of peripheral tissues, where they control immunity to foreign and self-antigens. The process of continuous DC renewal under homeostatic conditions is largely undefined. Here, we demonstrate that CD14+ DC precursors, either derived from CD34+ hematopoietic progenitor cells or isolated from blood, were attracted by the chemokine CXCL14, which is constitutively produced in healthy skin and other epithelial tissues.

Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues.

Antigen-driven T cell education and subsequent pathogen elimination present particular challenges for the immune system. Pathogens generally enter the body at peripheral sites such as the skin, gastrointestinal tract or lung, areas from which naïve T cells are largely excluded. Instead, naïve T cells constantly recirculate through secondary lymphoid organs, such as lymph nodes and Peyer's patches, in search for antigen brought to these locations by means of afferent lymphatic channels.

Chemokines: control of primary and memory T-cell traffic.

Motility is a hallmark of leukocytes, and breakdown in the control of migration contributes to many inflammatory diseases. Chemotactic migration of leukocytes largely depends on adhesive interaction with the substratum and recognition of a chemoattractant gradient. Chemokines are secreted proteins and have emerged as key controllers of integrin function and cell locomotion.

Characterization of human T cells that regulate neutrophilic skin inflammation.

It is unknown whether neutrophilic inflammations can be regulated by T cells. This question was analyzed by studying acute generalized exanthematous pustulosis (AGEP), which is a severe drug hypersensitivity resulting in intraepidermal or subcorneal sterile pustules. Recently, we found that drug-specific blood and skin T cells from AGEP patients secrete high levels of the potent neutrophil-attracting chemokine IL-8/CXCL8.

A skin-selective homing mechanism for human immune surveillance T cells.

Effective immune surveillance is essential for maintaining protection and homeostasis of peripheral tissues. However, mechanisms controlling memory T cell migration to peripheral tissues such as the skin are poorly understood. Here, we show that the majority of human T cells in healthy skin express the chemokine receptor CCR8 and respond to its selective ligand I-309/CCL1.