Marie N. Kolopp-Sarda

Modulation of the triggering receptor expressed on the myeloid cell type 1 pathway in murine septic shock.

ABSTRACT The triggering receptor expressed on myeloid cell type 1 (TREM-1) is a cell surface molecule that has been identified on both human and murine polymorphonuclear neutrophils and mature monocytes. The activation of TREM-1 in the presence of microbial components amplifies the inflammatory response and may be responsible for the hyperresponsiveness observed during the initial stage of sepsis. To investigate the effect of the modulation of the TREM-1 pathway during experimental murine sepsis, we used analogue synthetic peptides derived from the extracellular moiety of TREM-1. The TREM-1 ligand was expressed on both peritoneal and peripheral neutrophils during experimental peritonitis in mice. The TREM-1 peptides inhibited the recognition by TREM-1 of its ligand and protected endotoxinic mice from death. In septic rats, the TREM-1 peptides improved the hemodynamic status, attenuated the development of lactic acidosis, modulated the production of such proinflammatory cytokines as tumor necrosis factor alpha and interleukin-1β, and improved survival. The protective effect of these peptides on arterial pressure could partly be explained by a decreased production of nitric oxide. These data suggest that in vivo modulation of TREM-1 might be a suitable therapeutic tool for the treatment of sepsis.

Kinetics of specific salivary IgA responses in man after oral challenge by a ribosomal immunostimulant

The kinetics of specific IgA mucosal responses was assessed in 12 healthy volunteers over 3 weeks of treatment by oral administration of an immunostimulant, Ribomunyl, composed of ribosomes from the four bacteria Streptococcus pyogenes, Streptococcus pneumoniae, Klebsiella pneumoniae and Haemophilus influenzae. The levels of IgA specific for these four bacteria increased after each immunization and, after the third week of treatment, were significantly higher than baseline day 0 values. This study demonstrates that oral ribosomal immunostimulation results in the production of specific salivary antibodies liable to recognize whole bacteria antigens, and therefore likely to confer protection. The kinetic analysis performed also demonstrates the rapidity of specific mucosal immune responses after oral stimulation in man, a feature still seldom explored.

Anti-HBs cellular immune response in kidney recipients before and 4 months after transplantation.

ABSTRACT Patients with renal failure represent a population at risk for hepatitis B, since only 50 to 60% of them develop protective humoral responses after vaccination. As this could be due to an altered regulation of cellular immune responses, the objectives of the present study were to evaluate the proliferative abilities of lymphocytes from patients with chronic renal failure after stimulation in vitro with a mitogen (pokeweed mitogen [PWM]) or HBsAg. In order to differentiate between the immunodeficiency associated with renal failure and that due to immunosuppression posttransplantation, the same subjects were tested before and 4 months after kidney transplantation. The lymphoproliferation assay used was performed by flow cytometry, which is based on sequential analysis of the cell cycle and which allows analysis of cytokine production. Serologically, the group of 36 patients tested comprised 22% nonresponders, 30% poor responders, and 48% responders. Lymphocyte growth was observed for all patients after stimulation with PWM, indicating that these cells had the capacity to proliferate in vitro. The level of lymphoproliferation in response to PWM was significantly reduced after transplantation, yet both before and after transplantation, all serologic nonresponders developed cellular responses to at least two vaccines. No correlation between humoral and cellular responses was shown. Proliferating cells were lymphocytes, which mostly secreted interleukin 4 (IL-4) and IL-10 for the three serologic groups. This study suggests that even when repeated vaccination fails to induce significant antibody levels in patients with renal failure, specific HBs cellular responses develop, and these may prove to be efficient in protecting these patients against hepatitis B.

Mouse Lung Immune Response after Acute Exposure to Flour Dust

To approach the physiopathology of the mucosal immune response in flour-mill and bakery workers, the authors developed a mouse model, which allowed them to study immune responses induced in the deep lung by acute inhalation of flour dust. In situ quantification of T lymphocytes (Thy1-2) and T-cell subsets (CD4 and CD8), macrophages, B lymphocytes, and immunoglobulin A plasma cells in the lungs of all animals revealed significant modifications of these cell compartments as early as 3 d after exposure; within 10 d of exposure, levels returned to baseline. The data suggest that the lung could be a sensitive target for inhaled xenobiotics, which might generate rapid immune local modifications that result in the maintenance of homeostasis.

Kinetics of local immune responses in mouse Peyer's patches after respiratory exposure to flour

Peyers patches play a major role in the initiation of mucosal immune responses since most environmental antigens gain access to the digestive tract and are therefore liable to achieve contact with their specialized dome epithelium. We investigated kinetics of immunophenotypic modifications induced in the cells from murine Peyers patches in a model of intensive controlled exposure to flour dust. Three groups of mice were placed in an atmosphere enriched in wheat flour for 3, 6 or 10 consecutive days. Although Ig bearing B cell numbers did not vary, the numbers of IgA-containing plasma-cells increased significantly during the course of exposure. A significant and increasing imbalance of the CD4/CD8 ratio was noted, as early as after 3 days of exposure related both to increasing numbers of CD4+ and decreasing numbers of CD8+ cells. These data indicate a rapid kinetics of immune responses in Peyers patches in an original model of controlled respiratory challenge.