A pilot metagenomic study reveals that community derived mobile phones are reservoirs of viable pathogenic microbes

There is increasing attention focussed on the risks associated with mobile phones possibly serving as ‘Trojan Horse’ fomites for microbial transmission in healthcare settings. However, little is reported on the presence of microbes on community derived mobile phones which in 2021, numbered in the billions in circulation with majority being used on a daily basis. Identify viable microbial organisms swabbed from smartphones on a university campus. Entire surfaces of 5 mobile phones were swabbed and examined for their microbial content using pre-agar-based growths followed by downstream DNA metagenomic next-generation sequencing analysis. All phones were contaminated with viable microbes. 173 bacteria, 8 fungi, 8 protists, 53 bacteriophages, 317 virulence factor genes and 41 distinct antibiotic resistant genes were identified. While this research represents a pilot study, the snapshot metagenomic analysis of samples collected from the surface of mobile phones has revealed the presence of a large population of viable microbes and an array of antimicrobial resistant factors. With billions of phones in circulation, these devices might be responsible for the rise of community acquired infections. These pilot results highlight the importance of public health authorities considering mobile phones as ‘Trojan Horse’ devices for microbial transmission and ensure appropriate decontamination campaigns are implemented

Inverse correlation between IL-7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulation

Persistence is a hallmark of infection by viruses such as HIV, hepatitis B virus, hepatitis C virus and LCMV. In the case of LCMV, persistence may often be associated with exhaustion of CD8(+) T cells. We demonstrate here that persistent antigen suppressed IL-7Ralpha expression and this correlated with T cell exhaustion and reduced expression of the anti-apoptotic molecule B cell leukemia/lymphoma 2 (Bcl-2). In contrast, exposure to short-lived antigen only temporarily suppressed IL-7Ralpha expression, failed to induce T cell exhaustion, and primed T cells. Persistent antigen also suppressed IL-7Ralpha expression on primed T cells and this correlated with exhaustion of a previously stable primed T cell population. These findings suggest that antigen longevity regulates T cell fate

Differences in allergen-induced T cell activation between allergic asthma and rhinitis: Role of CD28, ICOS and CTLA-4

<p>Abstract</p> <p>Background</p> <p>Th2 cell activation and T regulatory cell (Treg) deficiency are key features of allergy. This applies for asthma and rhinitis. However with a same atopic background, some patients will develop rhinitis and asthma, whereas others will display rhinitis only. Co-receptors are pivotal in determining the type of T cell activation, but their role in allergic asthma and rhinitis has not been explored. Our objective was to assess whether allergen-induced T cell activation differs from allergic rhinitis to allergic rhinitis with asthma, and explore the role of ICOS, CD28 and CTLA-4.</p> <p>Methods</p> <p>T cell co-receptor and cytokine expressions were assessed by flow cytometry in PBMC from 18 house dust mite (HDM) allergic rhinitics (R), 18 HDM allergic rhinitics and asthmatics (AR), 13 non allergic asthmatics (A) and 20 controls, with or without anti-co-receptors antibodies.</p> <p>Results</p> <p>In asthmatics (A+AR), a constitutive decrease of CTLA-4+ and of CD4+CD25+Foxp3+ cells was found, with an increase of IFN-γ+ cells. In allergic subjects (R + AR), allergen stimulation induced CD28 together with IL-4 and IL-13, and decreased the proportion of CTLA-4+, IL-10+ and CD4+CD25+Foxp3+ cells. Anti-ICOS and anti-CD28 antibodies blocked allergen-induced IL-4 and IL-13. IL-13 production also involved CTLA-4.</p> <p>Conclusions</p> <p>T cell activation differs between allergic rhinitis and asthma. In asthma, a constitutive, co-receptor independent, Th1 activation and Treg deficiency is found. In allergic rhinitis, an allergen-induced Treg cell deficiency is seen, as well as an ICOS-, CD28- and CTLA-4-dependent Th2 activation. Allergic asthmatics display both characteristics.</p

A Gamma Interferon Independent Mechanism of CD4 T Cell Mediated Control of M. tuberculosis Infection in vivo

CD4 T cell deficiency or defective IFNγ signaling render humans and mice highly susceptible to Mycobacterium tuberculosis (Mtb) infection. The prevailing model is that Th1 CD4 T cells produce IFNγ to activate bactericidal effector mechanisms of infected macrophages. Here we test this model by directly interrogating the effector functions of Th1 CD4 T cells required to control Mtb in vivo. While Th1 CD4 T cells specific for the Mtb antigen ESAT-6 restrict in vivo Mtb growth, this inhibition is independent of IFNγ or TNF and does not require the perforin or FAS effector pathways. Adoptive transfer of Th17 CD4 T cells specific for ESAT-6 partially inhibited Mtb growth while Th2 CD4 T cells were largely ineffective. These results imply a previously unrecognized IFNγ/TNF independent pathway that efficiently controls Mtb and suggest that optimization of this alternative effector function may provide new therapeutic avenues to combat Mtb through vaccination

The Acute Environment, Rather than T Cell Subset Pre-Commitment, Regulates Expression of the Human T Cell Cytokine Amphiregulin

Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals. We showed previously that the epidermal growth factor family member Amphiregulin is expressed by T cell receptor-activated mouse CD4 T cells, particularly Th2 cells, and helps eliminate helminth infection. Here we report a detailed analysis of the regulation of Amphiregulin expression by human T cell subsets. Signaling through the T cell receptor induced Amphiregulin expression by most or all T cell subsets in human peripheral blood, including naive and memory CD4 and CD8 T cells, Th1 and Th2 in vitro T cell lines, and subsets of memory CD4 T cells expressing several different chemokine receptors and cytokines. In these different T cell types, Amphiregulin synthesis was inhibited by an antagonist of protein kinase A, a downstream component of the cAMP signaling pathway, and enhanced by ligands that increased cAMP or directly activated protein kinase A. Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines. Thus, in contrast to mouse T cells, Amphiregulin synthesis by human T cells is regulated more by acute signals than pre-commitment of T cells to a particular cytokine pattern. This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses

Memory Phenotype CD4 T Cells Undergoing Rapid, Nonburst-Like, Cytokine-Driven Proliferation Can Be Distinguished from Antigen-Experienced Memory Cells

Contrary to the current paradigm that nearly all memory T cells proliferate in response to antigenic stimulation, this paper shows that an important population of CD4 T lymphocytes achieves memory/effector status independent of antigenic stimulation

Inducible Costimulator Expression Regulates the Magnitude of Th2-Mediated Airway Inflammation by Regulating the Number of Th2 Cells

Inducible Costimulator (ICOS) is an important regulator of Th2 lymphocyte function and a potential immunotherapeutic target for allergy and asthma. A SNP in the ICOS 5' promoter in humans is associated with increased atopy and serum IgE in a founder population and increased ICOS surface expression and Th2 cytokine production from peripheral blood mononuclear cells. However, it is unknown if increased ICOS expression contributes to disease progression or is a result of disease pathology.We developed a mouse model in which ICOS surface expression levels are genetically predetermined to test our hypothesis that genetic regulation of ICOS expression controls the severity of Th2 responses in vivo. Using ICOS+/+ and ICOS+/- mice in a Th2 model of airway inflammation, we found that T cells from the ICOS+/- mice had reduced ICOS expression and decreased Th2-mediated inflammation in vivo. Although the activation status of the T cells did not differ, T cells isolated from the lungs and draining lymph nodes of ICOS+/- mice at the peak of inflammation produced less Th2 cytokines upon stimulation ex vivo. Using 4get mice, which express GFP upon IL-4 transcription, we determined that the decreased Th2 cytokines in ICOS+/- is due to reduced percentage of Th2 cells and not a defect in their ability to produce IL-4.These data suggest that in both mice and humans, the level of ICOS surface expression regulates the magnitude of the in vivo Th2 response, perhaps by influencing Th2 differentiation

Soluble ST2 plasma concentrations predict mortality in severe sepsis

Patients with sepsis-after surviving the initial hyperinflammatory phase-display features consistent with immunosuppression, including hyporesponsiveness of immunocompetent cells to bacterial agents. Immunosuppression is thought to be facilitated by negative regulators of toll-like receptors, including membrane-bound ST2. We investigated the release of soluble ST2 (sST2), a decoy receptor that inhibits membrane-bound ST2 signaling, during sepsis. The study population comprised 95 patients with severe sepsis admitted to one of two intensive care units (ICUs) at the day the diagnosis of severe sepsis was made. Blood was obtained daily from admission (day 0) until day 7 and finally at day 14. Twenty-four healthy subjects served as controls. sST2 and cytokines were measured in serum. Mortality among patients was 34% in the ICU and 45% in the hospital. On admission, sepsis patients had higher sST2 levels [10,989 (7,871-15,342) pg/ml, geometric mean (95% confidence interval, CI)] than controls [55 (20-145) pg/ml, P < 0.0001]. Serum sST2 remained elevated in patients from day 0 to 14 and correlated with disease severity scores (P < 0.001) and cytokine levels on day 0 and during course of disease (P < 0.0001). Nonsurvivors displayed elevated sST2 levels compared with survivors of the intensive care unit (P < 0.0001). Sepsis results in sustained elevation of serum sST2 levels, which correlates with disease severity and mortalit