Current concepts of immune dysregulation in cystic fibrosis.

Cystic fibrosis (CF) lung disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene and is characterized by a perpetuated feedback loop of bacterial infection and inflammation. Both intrinsic (CFTR-dependent) and extrinsic (CFTR-independent) mechanisms contribute to the inflammatory phenotype of CF lung disease. Innate immune cells, initially recruited to combat bacterial pathogens, are acting in a dysregulated and non-resolving fashion in CF airways and cause harm to the host by releasing proteases and oxidants. Targeting harmful immune pathways, while preserving protective ones, remains the challenge for the future. This review highlights current concepts of innate immune dysregulation in CF lung disease.

Extracorporeal photopheresis increases neutrophilic myeloid-derived suppressor cells in patients with GvHD.

Extracorporeal photopheresis (ECP) is beneficial in patients with T-cell-mediated disorders, including GvHD, but the underlying immunological mechanisms are incompletely understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterized by their capacity to suppress T-cell proliferation. We quantified MDSCs by flow cytometry in peripheral blood from patients after BMT with GvHD before and after ECP treatment, patients after BMT but without GvHD and age-matched healthy controls. MDSC functionality was analyzed using T-cell proliferation, cytokine release and arginase activity. GvHD patients showed increased baseline percentages of neutrophilic MDSCs (PMN-MDSCs) compared with healthy controls and patients after BMT without GvHD. ECP treatment in GvHD patients rapidly increased circulating percentages of PMN-MDSCs. Functionally, PMN-MDSCs efficiently dampened Th1 and Th17 responses and were paralleled by an increase of cellular and extracellular arginase activity. Following ECP longitudinally over 16 weeks, two GvHD responder subgroups were identified, with group one continuously increasing PMN-MDSCs and group two with stable or decreasing PMN-MDSCs over time. This study demonstrates for the first time that ECP increases T-cell-dampening PMN-MDSCs in GvHD patients, a finding that should be confirmed in larger series of GvHD patients.

Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses.

Neonates show an impaired anti-microbial host defence, but the underlying immune mechanisms are not understood fully. Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell subset characterized by their capacity to suppress T cell immunity. In this study we demonstrate that a distinct MDSC subset with a neutrophilic/granulocytic phenotype (Gr-MDSCs) is highly increased in cord blood compared to peripheral blood of children and adults. Functionally, cord blood isolated Gr-MDSCs suppressed T cell proliferation efficiently as well as T helper type 1 (Th1), Th2 and Th17 cytokine secretion. Beyond T cells, cord blood Gr-MDSCs controlled natural killer (NK) cell cytotoxicity in a cell contact-dependent manner. These studies establish neutrophilic Gr-MDSCs as a novel immunosuppressive cell subset that controls innate (NK) and adaptive (T cell) immune responses in neonates. Increased MDSC activity in cord blood might serve as key fetomaternal immunosuppressive mechanism impairing neonatal host defence. Gr-MDSCs in cord blood might therefore represent a therapeutic target in neonatal infections.

Differences of IgG antibody avidity after an acellular pertussis (aP) booster in adolescents after a whole cell (wcP) or aP primary vaccination.

Compared to whole cell pertussis (wcP) vaccines, acellular pertussis vaccines (aP) have a better safety profile with lower reactogenicity, although their short and long-term efficacy was found to be slightly lower. Up to now, no established serological parameter to predict long-term protection exists. IgG-anti-pertussis avidity possibly determines the effect of different pertussis vaccines and boosting intervals on long-term immunity. Thus, the avidity of a tetanus-diphtheria-aP booster at 10-14 years was tested in three groups of adolescents who had been previously immunized with either five doses of aP (5aP) at 2, 4, 6, 15-18 months and 5-6 years of age, four doses of aP (4aP) or four doses of wcP (4wcP) at 2, 4, 6 and 15-18 months of age. Relative avidity index (RAI) of IgG-anti-pertussis toxin (PT) and IgG-anti-filamentous-hemagglutinin (FHA) was assessed by an adapted ELISA. RAI of IgG-anti-PT and of IgG-anti-FHA correlated positively with antibody concentrations in the pre-vaccination and in the post-vaccination analysis and significantly increased after adolescent booster with aP in all groups. Pre- and post-vaccination, the proportion of participants with IgG-anti-PT RAI>40% (moderate to high avidity) was significantly lower in the 4wcP group (52.9% and 88.9%) compared to the 5aP group (89.5% and 100.0%). In conclusion, TdaP in adolescence induces an increase of antibody avidity and, thus, is able to enhance the binding-quality of antibodies against pertussis. The study suggests including antibody avidity into serological studies on the humoral response to provide information about the long-term efficacy of the vaccine.

[Psychotherapy and obesity: strategies, challenges and possibilities]. / Psychotherapie und Adipositas : Strategien, Herausforderungen und Chancen.

One fifth of the German population is obese with increasing prevalence. Psychotherapy plays an important role in weight loss programmes. Cognitive behaviour therapy, targeting lifestyle changes, including exercise and eating behaviour, is the evidence-based treatment of choice. Especially the lack of motivation or absence of weight loss, further weight gain or psychosocial burden makes psychotherapy essential. The treatment of a comorbid binge eating disorder should be initiated prior to focusing on weight loss. Remarkably difficult stages in the treatment of obesity are the initiation of changes as well as the maintenance of the achieved weight loss. Internet-based attempts will become increasingly important.

Acute tryptophan depletion increases experimental nausea but also induces hunger in healthy female subjects.

BACKGROUND: Acute tryptophan depletion (ATD) is an experimental model to reduce central serotonin levels. METHODS: Thirty-eight healthy female subjects were randomly assigned to two groups (ATD and control) in a randomized, double-blinded parallel-group design. Following a standardized and balanced amino acid diet (including 1.21 g tryptophan) on the first day, they received either a protein drink without tryptophan (but substituted by other amino acids) (ATD condition) or the balanced protein drink with tryptophan (control condition) 24 h later. Four hours after its consumption, they were exposed to a standard rotation procedure. Symptom ratings (SR), ratings of hunger and mood scores were taken prior to rotation, at each break, and 15 and 30 min thereafter, together with saliva cortisol samples. KEY RESULTS: Five subjects could not tolerate the entire rotation procedure and were excluded from analysis. For the remaining n = 33, SR and hunger ratings were higher during ATD than during control conditions, but mood was unaffected. Cortisol levels rose significantly with rotation but were unaffected by ATD. High baseline cortisol levels were associated with lower SR during rotation. The protective effects of morning cortisol were pronounced during the menstrual and follicular phase of the cycle and not present during ovulation and the luteal phase. CONCLUSIONS & INFERENCES: Acute tryptophan depletion is associated with increased symptoms of nausea in healthy female subjects when exposed to body rotation. Acute tryptophan depletion also increases hunger rating. These opposite effects may indicate independent actions of the serotonin on central and peripheral functions.