- Association of CCL2 with systemic inflammation in Schnitzler's syndrome. [Journal Article]
- BJBr J Dermatol 2018 Oct 19
- CONCLUSIONS: CCL2 may be an important component of the pathogenetic cascade leading to bone alterations and a suitable marker of disease activity in patients with SchS. This article is protected by copyright. All rights reserved.
- DNGR-1 in dendritic cells limits tissue damage by dampening neutrophil recruitment. [Journal Article]
- SciScience 2018 Oct 19; 362(6412):351-356
- Host injury triggers feedback mechanisms that limit tissue damage. Conventional type 1 dendritic cells (cDC1s) express dendritic cell natural killer lectin group receptor-1 (DNGR-1), encoded by the g...
Host injury triggers feedback mechanisms that limit tissue damage. Conventional type 1 dendritic cells (cDC1s) express dendritic cell natural killer lectin group receptor-1 (DNGR-1), encoded by the gene Clec9a, which senses tissue damage and favors cross-presentation of dead-cell material to CD8+ T cells. Here we find that DNGR-1 additionally reduces host-damaging inflammatory responses induced by sterile and infectious tissue injury in mice. DNGR-1 deficiency leads to exacerbated caerulein-induced necrotizing pancreatitis and increased pathology during systemic Candida albicans infection without affecting fungal burden. This effect is B and T cell-independent and attributable to increased neutrophilia in DNGR-1-deficient settings. Mechanistically, DNGR-1 engagement activates SHP-1 and inhibits MIP-2 (encoded by Cxcl2) production by cDC1s during Candida infection. This consequently restrains neutrophil recruitment and promotes disease tolerance. Thus, DNGR-1-mediated sensing of injury by cDC1s serves as a rheostat for the control of tissue damage, innate immunity, and immunopathology.
- Murine myeloproliferative disorder as a consequence of impaired collaboration between dendritic cells and CD4 T cells. [Journal Article]
- BloodBlood 2018 Oct 17
- Dendritic cells (DCs) are a key cell type in the initiation of the adaptive immune response. Recently an additional role for DCs in suppressing myeloproliferation was discovered. Myeloproliferative d...
Dendritic cells (DCs) are a key cell type in the initiation of the adaptive immune response. Recently an additional role for DCs in suppressing myeloproliferation was discovered. Myeloproliferative disorder (MPD) was observed in both murine studies with constitutive depletion of DCs, and in patients with congenital deficiency in DCs caused by mutations in GATA2 or IRF8 The mechanistic link between DC deficiency and MPD was not predicted through the known biology and has remained an enigma. Prevailing models suggest numerical DC deficiency leads to MPD through compensatory myeloid differentiation. Here we formally tested whether MPD can also arise through a loss of DC function without numerical deficiency. Using mice where DCs are deficient in antigen presentation, we find spontaneous myeloproliferative disorder characterized by splenomegaly, neutrophilia and extramedullary hematopoiesis, despite normal numbers of DCs. Disease development was dependent on loss of the MHC class II antigen presenting complex on DCs and was eliminated in mice deficient in total lymphocytes. Mice lacking both MHCII and CD4 T cells did not develop disease. MPD was thus paradoxically contingent on both the presence of CD4 T cells and on a failure of DCs to activate CD4 T cells, trapping the cells in a naïve Flt3L-expressing state. These results identify a novel requirement for intercellular collaboration between dendritic cells and CD4 T cells to regulate myeloid differentiation. Our findings support a new conceptual framework of DC biology in preventing MPD in mice and humans.
- Lung Function Trajectory Types in Never-Smoking Adults With Asthma: Clinical Features and Inflammatory Patterns. [Journal Article]
- AAAllergy Asthma Immunol Res 2018; 10(6):614-627
- CONCLUSIONS: Trajectory clustering analysis of FEV1 identified 5 distinct types, representing well-preserved to severely decreased FEV1. Persistent airflow obstruction may be related to non-atopy, a low IgE level, and older age accompanied by neutrophilic inflammation and low baseline FEV1 levels.
- Neutrophilia as prognostic biomarker in locally advanced stage III lung cancer. [Journal Article]
- PlosPLoS One 2018; 13(10):e0204490
- CONCLUSIONS: In stage III NSCLC patients, treated with concurrent cisplatin-based chemoradiation, baseline leukocytosis and neutrophilia were associated with worse OS, PFS, LRC, and DMC. In addition with previously available markers, this independent cost-effective biomarker could help to stratify stage III NSCLC population with more accuracy.
- Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis. [Journal Article]
- MBIOMBio 2018 Oct 09; 9(5)
- Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are observed in severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. SARS-CoV emerged in 20...
Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are observed in severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. SARS-CoV emerged in 2002 to 2003 and led to a global outbreak of SARS. As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Using this model, we investigated the role of the complement system during SARS-CoV infection. We observed activation of the complement cascade in the lung as early as day 1 following SARS-CoV infection. To test whether this activation contributed to protective or pathologic outcomes, we utilized mice deficient in C3 (C3-/-), the central component of the complement system. Relative to C57BL/6J control mice, SARS-CoV-infected C3-/- mice exhibited significantly less weight loss and less respiratory dysfunction despite equivalent viral loads in the lung. Significantly fewer neutrophils and inflammatory monocytes were present in the lungs of C3-/- mice than in C56BL/6J controls, and subsequent studies revealed reduced lung pathology and lower cytokine and chemokine levels in both the lungs and the sera of C3-/- mice than in controls. These studies identify the complement system as an important host mediator of SARS-CoV-induced disease and suggest that complement activation regulates a systemic proinflammatory response to SARS-CoV infection. Furthermore, these data suggest that SARS-CoV-mediated disease is largely immune driven and that inhibiting complement signaling after SARS-CoV infection might function as an effective immune therapeutic.IMPORTANCE The complement system is a critical part of host defense to many bacterial, viral, and fungal infections. It works alongside pattern recognition receptors to stimulate host defense systems in advance of activation of the adaptive immune response. In this study, we directly test the role of complement in SARS-CoV pathogenesis using a mouse model and show that respiratory disease is significantly reduced in the absence of complement even though viral load is unchanged. Complement-deficient mice have reduced neutrophilia in their lungs and reduced systemic inflammation, consistent with the observation that SARS-CoV pathogenesis is an immune-driven disease. These data suggest that inhibition of complement signaling might be an effective treatment option following coronavirus infection.
- Splenectomy modulates early immuno-inflammatory responses to trauma-hemorrhage and protects mice against secondary sepsis. [Journal Article]
- SRSci Rep 2018 Oct 05; 8(1):14890
- In polytrauma patients, the impact of splenectomy is equivocal, ranging from negative to protective. We investigated the impact of splenectomy on immune responses in the 1st-hit polytrauma alone and ...
In polytrauma patients, the impact of splenectomy is equivocal, ranging from negative to protective. We investigated the impact of splenectomy on immune responses in the 1st-hit polytrauma alone and on survival in the post-traumatic sepsis (2nd hit). Female BALB/c mice underwent polytrauma (1st hit) consisting of either a) TH: femur fracture, hemorrhagic shock or b) TSH: splenectomy, femur fracture, hemorrhagic shock. Additionally, the polytrauma hit was followed by cecal ligation and puncture (CLP) 48 h later and compared to CLP alone. Splenectomy improved the 28-day survival in secondary sepsis to 92% (from 62%), while TH lowered it to 46% (p < 0.05). The improved survival was concurrent with lower release of inflammatory cytokines (IL-6, CXCL-1, MCP-1) and increase of C5a post-CLP. In the polytrauma hit alone, TSH induced stronger neutrophilia (1.9 fold) and lymphocytosis (1.7 fold) when compared to TH mice. Moreover, TSH resulted in a 41% rise of regulatory T-cells and reduced the median fluorescence intensity of MHC-2 on monocytes by 55% within 48 h (p < 0.05). Conversely, leukocyte phagocytic capacity was significantly increased by 4-fold after TSH despite a similar M1/M2 macrophage profile in both groups. Summarizing, splenectomy provoked both immuno-suppressive and immuno-stimulatory responses but was life-saving in secondary sepsis. Additionally, the polytrauma components in 2-hit models should be tested for their effects on outcome; the presumed end-effect of the 1st hit solely based on the common immuno-inflammatory parameters could be misleading.
- An old disease re-emerging: acute rheumatic fever. [Journal Article]
- CMClin Med (Lond) 2018; 18(5):400-402
- We present the case of a 41-year-old Australian woman with a 3-day history of fevers and migratory polyarthritis. Three weeks prior she had been treated by her GP with phenoxymethylpenicillin for acu...
We present the case of a 41-year-old Australian woman with a 3-day history of fevers and migratory polyarthritis. Three weeks prior she had been treated by her GP with phenoxymethylpenicillin for acute tonsillitis. Examination confirmed synovitis. Systemic assessment including cardiovascular, neurological and skin examination was unremarkable. Abnormal investigations included a leucocytosis with neutrophilia, C-reactive peptide of 116 mg/L, erythrocyte sedimentation rate of 103 mm/hour and acute transaminitis. The antistreptolysin O titre was 304 IU, which increased to 1,250 IU after 2 weeks. Troponin T, electrocardiogram and echocardiography were all normal. The patient was treated for acute rheumatic fever with corticosteroids and a 10-day course of cephalexin. After 8 weeks, she made a full recovery and had normalised inflammatory markers and liver biochemistry. She was then commenced on monthly prophylactic intramuscular benzathine penicillin. This case study aims to raise awareness of the presentation, diagnosis and management of acute rheumatic fever.
- Development of membranoproliferative glomerulonephritis-like glomerulopathy in a patient with neutrophilia resulting from endogenous granulocyte-colony stimulating factor overproduction: a case report. [Journal Article]
- BNBMC Nephrol 2018 Oct 04; 19(1):251
- CONCLUSIONS: The unique features of this case suggest that endogenous overproduction of G-CSF could play an important role in the pathogenesis of active glomerulonephritis.
New Search Next
- Utility and Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Dogs with Septic Peritonitis. [Journal Article]
- JAJ Am Anim Hosp Assoc 2018 Oct 01
- Systemic inflammation is known to cause WBC abnormalities, specifically neutrophilia and lymphopenia. The neutrophil-to-lymphocyte ratio (NLR) is a simple and affordable biomarker that has been used ...
Systemic inflammation is known to cause WBC abnormalities, specifically neutrophilia and lymphopenia. The neutrophil-to-lymphocyte ratio (NLR) is a simple and affordable biomarker that has been used in human clinical settings of sepsis but has not been investigated in veterinary species. We evaluated NLR in dogs with septic and nonseptic systemic inflammatory diseases and compared with a healthy dog population. An NLR ≥6 had an 84.39% sensitivity and 86.95% specificity to identify dogs with systemic inflammatory states; however, no ratio distinguished septic and nonseptic causes. The NLR was not associated with length of hospitalization, morbidity based on the acute patient physiologic laboratory evaluation scoring system, or mortality. The disassociation may be due to the retrospective nature of the study, including a restricted population size and acquisition of only a one-time blood sample. NLR is currently of limited use for diagnosis and prognosis in systemic inflammatory states in dogs, and larger, prospective studies are necessary to further evaluate NLR.