A cross-species interaction with a symbiotic commensal enables cell-density-dependent growth and in vivo virulence of an oral pathogen

Recent studies describe in detail the shifts in composition of human-associated polymicrobial communities from health to disease. However, the specific processes that drive the colonization and overgrowth of pathogens within these communities remain incompletely understood. We used in vitro culture systems and a disease-relevant mouse model to show that population size, which determines the availability of an endogenous diffusible small molecule, limits the growth, colonization, and in vivo virulence of the human oral pathogen Porphyromonas gingivalis. This bacterial pathogen overcomes the requirement for an endogenous cue by utilizing a cell-density dependent, growth-promoting, soluble molecule provided by the symbiotic early colonizer Veillonella parvula, but not produced by other commensals tested. Our work shows that exchange of cell-density-dependent diffusible cues between specific early and late colonizing species in a polymicrobial community drives microbial successions, pathogen colonization and disease development, representing a target process for manipulation of the microbiome towards the healthy state

Abnormal macrophage response to microbial stimulus in a 43-year-old man with a severe form of atherosclerosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>New evidence indicates infections are emerging as risk factors for atherosclerosis although their specific role in the development and progression of atherosclerosis is still unclear.</p> <p>Case presentation</p> <p>A 43-year-old Caucasian man who had been treated for four years for multiple sclerosis progressively manifested systemic hypertension, polycythemia, peripheral arterial occlusion with intermittent claudication, and persistent headaches. In 2006, an instrumental analysis (magnetic resonance imaging) of our patient revealed widespread fibrocalcific atherosclerotic lesions which accounted for all his current symptoms, including those related to microbial stimulus. Two particular aspects were of interest, namely a lack of conventional cardiovascular risk factors and a negative family history for cardiovascular events. His chemical blood tests all yielded negative findings although a low positive hepatitis C virus-ribonucleic acid titer was detected. The titer had progressively increased and worsening atherosclerosis threatened the life of our patient. Interferon therapy was not appropriate for our patient due to the severe adverse effects observed shortly after its administration.</p> <p>Conclusions</p> <p>The reaction of individual cells to infections may provide an explanation as to why individuals with a similar microbial burden, corrected for the presence of other risk factors, display a different susceptibility to developing or worsening atherosclerosis. The identification of susceptible individuals and the treatment even of silent infections may provide an additional tool against atherosclerosis and its clinical complications. The evaluation of cell susceptibility before and after the correction of risk factors may contribute to the assessment of the efficacy of drug therapy.</p

Testing the theory of immune selection in cancers that break the rules of transplantation

Modification of cancer cells likely to reduce their immunogenicity, including loss or down-regulation of MHC molecules, is now well documented and has become the main support for the concept of immune surveillance. The evidence that these modifications, in fact, result from selection by the immune system is less clear, since the possibility that they may result from reorganized metabolism associated with proliferation or from cell de-differentiation remains. Here, we (a) survey old and new transplantation experiments that test the possibility of selection and (b) survey how transmissible tumours of dogs and Tasmanian devils provide naturally evolved tests of immune surveillance

The Acute Phase Protein Serum Amyloid A Induces Lipolysis and Inflammation in Human Adipocytes through Distinct Pathways

Background: The acute phase response (APR) is characterized by alterations in lipid and glucose metabolism leading to an increased delivery of energy substrates. In adipocytes, there is a coordinated decrease in Free Fatty acids (FFAs) and glucose storage, in addition to an increase in FFAs mobilization. Serum Amyloid A (SAA) is an acute phase protein mainly associated with High Density Lipoproteins (HDL). We hypothesized that enrichment of HDL with SAA, during the APR, could be implicated in the metabolic changes occurring in adipocytes. Methodology/Principal Findings: In vitro differentiated human adipocytes (hMADS) were treated with SAA enriched HDL or recombinant SAA and the metabolic phenotype of the cells analyzed. In hMADS, SAA induces an increased lipolysis through an ERK dependent pathway. At the molecular level, SAA represses PPARc2, C/EBPa and SREBP-1c gene expression, three transcription factors involved in adipocyte differentiation or lipid synthesis. In addition, the activation of the NF-kB pathway by SAA leads to the induction of pro-inflammatory cytokines and chemokines, as in the case of immune cells. These latter findings were replicated in freshly isolated mature human adipocytes. Conclusions/Significance: Besides its well-characterized role in cholesterol metabolism, SAA has direct metabolic effects on human adipocytes. These metabolic changes could be at least partly responsible for alterations of adipocyte metabolism observed during the APR as well as during pathophysiological conditions such as obesity and conditions leading to insuli

HIV-1 co-receptor usage:influence on mother-to-child transmission and pediatric infection

Viral CCR5 usage is not a predictive marker of mother to child transmission (MTCT) of HIV-1. CXCR4-using viral variants are little represented in pregnant women, have an increased although not significant risk of transmission and can be eventually also detected in the neonates. Genetic polymorphisms are more frequently of relevance in the child than in the mother. However, specific tissues as the placenta or the intestine, which are involved in the prevalent routes of infection in MTCT, may play an important role of selective barriers

The management of Sjogren&apos;s syndrome

Sjogren’s syndrome is a chronic autoimmune disorder, characterized by lymphocytic infiltration and malfunction of the exocrine glands, resulting in dry mouth and eyes. The syndrome can present either alone (primary Sjogren’s syndrome) or in the context of an underlying connective tissue disease (secondary Sjogren’s syndrome). Systemic features, resulting from cutaneous, respiratory, renal, hepatic, neurologic, and vascular involvement, often occur. Two types of primary Sjogren’s syndrome are currently recognized: a benign disease that affects quality of life, and a systemic syndrome associated with increased morbidity and mortality owing to a high risk of malignant transformation, and that requires close follow-up. Ocular involvement, manifested as keratoconjunctivitis sicca, is managed with local and systemic stimulators of tear secretion and supportive surgical procedures. Treatment of oral manifestations includes intense oral hygiene, prevention and treatment of oral infections, use of saliva substitutes, and local and systematic stimulation of salivary secretion. Cholinergic agents, such as pilocarpine and cevimeline, are helpful in patients with residual salivary function, and ciclosporin ocular drops seem to be of some benefit. Systemic immunosuppressives are reserved for treatment of severe extraglandular manifestations of Sjogren’s syndrome. Anti-B-cell therapy is a new potential therapy for the glandular and extraglandular manifestations, such as glomerulonephritis or vasculitis, in addition to the management of lymphoma associated with Sjogren’s syndrome. Induction of oral tolerance and gene-transfer modalities were recently attempted in animal models, with promising results