NK Cell Receptor NKp46 Regulates Graft-versus-Host Disease

SummaryHematopoietic stem cell transplantation (HSCT) is often the only curative treatment for a wide variety of hematologic malignancies. Donor selection in these diseases is crucial, given that transplanted cells can mediate not only the desired graft-versus-leukemia effect but also graft-versus-host disease (GVHD). Here, we demonstrate that in the absence of NKp46, a major killer receptor expressed by human and mouse natural killer (NK) cells, GVHD is greatly exacerbated, resulting in rapid mortality of the transplanted animals because of infection with commensal bacteria. Furthermore, we demonstrate that the exacerbated GVHD is the result of an altered ability of immune cells to respond to stimulation by immature dendritic cells. Because high and low expression of NKp46 on NK cells is observed in different individuals, our data indicate that choosing NKp46-high donors for the treatment of different hematologic malignancies might lead to better tumor eradication while minimizing GVHD

Mitral Stenosis Presenting with Acute Hearing Loss

A 47-year old woman presented with acute hearing loss, followed by dyspnea and then reduced consciousness and a hemiparesis. Investigations led to a diagnosis of cardiac emboli related to rheumatic mitral stenosis

Direct Recognition of Fusobacterium nucleatum by the NK Cell Natural Cytotoxicity Receptor NKp46 Aggravates Periodontal Disease

Periodontitis is a common human chronic inflammatory disease that results in the destruction of the tooth attachment apparatus and tooth loss. Although infections with periopathogenic bacteria such as Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum) are essential for inducing periodontitis, the nature and magnitude of the disease is determined by the host's immune response. Here, we investigate the role played by the NK killer receptor NKp46 (NCR1 in mice), in the pathogenesis of periodontitis. Using an oral infection periodontitis model we demonstrate that following F. nucleatum infection no alveolar bone loss is observed in mice deficient for NCR1 expression, whereas around 20% bone loss is observed in wild type mice and in mice infected with P. gingivalis. By using subcutaneous chambers inoculated with F. nucleatum we demonstrate that immune cells, including NK cells, rapidly accumulate in the chambers and that this leads to a fast and transient, NCR1-dependant TNF-α secretion. We further show that both the mouse NCR1 and the human NKp46 bind directly to F. nucleatum and we demonstrate that this binding is sensitive to heat, to proteinase K and to pronase treatments. Finally, we show in vitro that the interaction of NK cells with F. nucleatum leads to an NCR1-dependent secretion of TNF-α. Thus, the present study provides the first evidence that NCR1 and NKp46 directly recognize a periodontal pathogen and that this interaction influences the outcome of F. nucleatum-mediated periodontitis

Stromal Cell-Derived Factor 1 Mediates Immune Cell Attraction upon Urinary Tract Infection

Urinary tract infection (UTI) is the most common type of bacterial infection in humans. Fifty percent of all women will experience at least one UTI in their lifetime, with uropathogenic Escherichia coli (UPEC) accounting for 80% of reported cases. UTI evokes a complex, well-timed immune response that is crucial for bacterial clearance. The majority of immune cells participating in the immune response are absent from the healthy bladder, and the mechanisms used to recruit them upon UTI are not fully understood. Here, we show that immediately after UPEC infection, bladder epithelial cells secrete stromal cell-derived factor 1 (SDF-1), initiating immune cell accumulation at the site of infection. SDF-1 blockade significantly reduced immune cell migration to the infected bladder, resulting in severe exacerbation of infection. We also show that FimH, the adhesin of type 1 fimbria, one of UPEC’s virulence factors, is directly involved in the secretion of SDF-1 upon UTI

Angiography of the Left Posterior Circulation of the Brain

<p>Angiography (sagittal view) demonstrates complete occlusion of the left vertebral artery (black arrow).</p

Angiography of the Left Anterior Circulation of the Brain

<p>Angiography shows the left internal carotid artery with an occlusion of one of its main branches, the left MCA (arrow shows origin occluded by a thrombus).</p