Frontiers in immunology
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Frontiers in immunology · Jan 2017
Development of Three Different NK Cell Subpopulations during Immune Reconstitution after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Markers in GvHD and Viral Infections.
Natural killer (NK) cells play an important role following allogeneic hematopoietic stem cell transplantation (HSCT) exerting graft-versus-leukemia/tumor effect and mediating pathogen-specific immunity. Although NK cells are the first donor-derived lymphocytes reconstituting post-HSCT, their distribution of CD56++CD16- (CD56bright), CD56++CD16+ (CD56intermediate=int), and CD56+CD16++ (CD56dim) NK cells is explicitly divergent from healthy adults, but to some extent comparable to the NK cell development in early childhood. The proportion of CD56bright/CD56int/CD56dim changed from 15/8/78% in early childhood to 6/4/90% in adults, respectively. ⋯ Furthermore, a prolonged and elevated peak in CD56int NK cells seemed to be characteristic for the chronification of GvHD. In context of viral infection, a slightly lower CD56 and CD16 receptor expression followed by a considerable reduction in the absolute CD56dim NK cell numbers combined with reoccurrence of CD56int NK cells was observed. Our results suggest that a precise analysis of the reconstitution of NK cell subpopulations post-HSCT might indicate the occurrence of undesired events post-HSCT such as severe aGvHD.
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Frontiers in immunology · Jan 2017
Immune Responses to Broad-Spectrum Antibiotic Treatment and Fecal Microbiota Transplantation in Mice.
Compelling evidence demonstrates the pivotal role of the commensal intestinal microbiota in host physiology and the detrimental effects of its perturbations following antibiotic treatment. Aim of this study was to investigate the impact of antibiotics induced depletion and subsequent restoration of the intestinal microbiota composition on the murine mucosal and systemic immunity. To address this, conventional C57BL/6j mice were subjected to broad-spectrum antibiotic treatment for 8 weeks. ⋯ These effects were, however, completely restored upon FMT. In summary, broad-spectrum antibiotic treatment resulted in profound local (i.e., small and large intestinal), peripheral (i.e., MLN), and systemic (i.e., splenic) changes in the immune cell repertoire that could, at least in part, be restored upon FMT. Further studies need to unravel the distinct molecular mechanisms underlying microbiota-driven changes in immune homeostasis subsequently providing novel therapeutic or even preventive approaches in human immunopathologies.
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Frontiers in immunology · Jan 2017
Intracellular S100A9 Promotes Myeloid-Derived Suppressor Cells during Late Sepsis.
Myeloid precursor cell reprogramming into a myeloid-derived suppressor cell (MDSC) contributes to high mortality rates in mouse and human sepsis. S100A9 mRNA and intracellular protein levels increase during early sepsis and remain elevated in Gr1+CD11b+ MDSCs after pro-inflammatory sepsis transitions to the later chronic anti-inflammatory and immunosuppressive phenotype. The purpose of this study was to determine whether intracellular S100A9 protein might sustain Gr1+CD11b+ MDSC repressor cell reprogramming during sepsis. ⋯ Surprisingly, we find that intracellular S100A9 protein translocates from the cytosol to nucleus in Gr1+CD11b+ MDSCs during late sepsis and promotes expression of miR-21 and miR-181b immune repressor mediators. We further provide support of this immunosuppression pathway in human sepsis. This study may inform a new therapeutic target for improving sepsis outcome.
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Frontiers in immunology · Jan 2017
Forebrain Cholinergic Dysfunction and Systemic and Brain Inflammation in Murine Sepsis Survivors.
Sepsis, a complex disorder characterized by immune, metabolic, and neurological dysregulation, is the number one killer in the intensive care unit. Mortality remains alarmingly high even in among sepsis survivors discharged from the hospital. There is no clear strategy for managing this lethal chronic sepsis illness, which is associated with severe functional disabilities and cognitive deterioration. ⋯ Furthermore, microglial activation was linked to decreased cortical ChAT protein expression and increased AChE activity. These results reinforce the notion of persistent inflammation-immunosuppression and catabolic syndrome in sepsis survivors and characterize a previously unrecognized relationship between forebrain cholinergic dysfunction and neuroinflammation in sepsis survivors. This insight is of interest for new therapeutic approaches that focus on brain cholinergic signaling for patients with chronic sepsis illness, a problem with no specific treatment.
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Frontiers in immunology · Jan 2017
Risk Factors for Intensive Care Unit Admission in Patients with Autoimmune Encephalitis.
Prevention and early recognition of critical illness in patients with autoimmune encephalitis (AE) is essential to achieve better outcome. ⋯ We confirmed the need for ICU care in a subgroup of patients and the prevailing objective is improved seizure control, and definite diagnosis of AE and anemia were identified as risk factors for development of critical illness. However, prognosis was not affected by ICU admission.