Suppression of SIV-specific CD4+ T cells by infant but not adult macaque regulatory T cells: implications for SIV disease progression.

The impact of regulatory T cells (T reg cells) on the course of HIV and SIV disease is unknown. T reg cells could suppress protective antiviral responses and accelerate disease progression. Alternatively, these cells might block T cell activation and thereby limit viral replication as well as activation-associated immunopathology. Given the higher frequency of T reg cells known to be present during human fetal ontogeny, such influences may be most important in the context of perinatal infection. We found that infant macaques had higher fractions of CD4(+)CD25(+)CD127(low)FoxP3(+) T reg cells in the peripheral blood and in lymphoid tissues, and that these T reg cells showed greater in vitro suppressive activity on a per cell basis. Infant and adult macaques were infected with SIVmac251 to test the influence of the T reg cell compartment on SIV-specific immune responses. After infection with SIV, most (three out of four) infant macaques had persistently high viral loads, weak and transient SIV-specific CD4(+) and CD8(+) T cell responses, and rapid disease progression. T reg cells in the infant but not in the adult directly suppressed SIV-specific CD4(+) T cell responses, which were detectable only after depletion of T reg cells. In the case of both the infant and the adult macaque, T reg cells were not able to directly suppress SIV-specific CD8(+) T cell responses and had no apparent effect on T cell activation. In aggregate, these observations suggest that the T reg cell compartment of the infant macaque facilitates rapid disease progression, at least in part by incapacitating SIV-specific CD4(+) T cell responses

Immune responses and HIV: a little order from the chaos

HIV is evolution gone mad and bad. The virus infects a person and rapidly diversifies to become a huge swarm of viruses, each equipped differently to resist the onslaught of diverse T cells and antibodies. We can't expect to predict details of the struggle between virus and immunity, right? Wrong—maybe we can make some predictions, say two new landmark studies with potentially huge consequences for AIDS vaccine design

Persistent effects of early infant diet and associated microbiota on the juvenile immune system.

Early infant diet has significant impacts on the gut microbiota and developing immune system. We previously showed that breast-fed and formula-fed rhesus macaques develop significantly different gut microbial communities, which in turn are associated with different immune systems in infancy. Breast-fed animals manifested greater T cell activation and proliferation and harbored robust pools of T helper 17 (TH17) cells. These differences were sustained throughout the first year of life. Here we examine groups of juvenile macaques (approximately 3 to 5 y old), which were breast-fed or formula-fed in infancy. We demonstrate that juveniles breast-fed in infancy maintain immunologic differences into the fifth year of life, principally in CD8(+) memory T cell activation. Additionally, long-term correlation networks show that breast-fed animals maintain persistent relationships between immune subsets that are not seen in formula-fed animals. These findings demonstrate that infant feeding practices have continued influence on immunity for up to 3 to 5 y after birth and also reveal mechanisms for microbial modulation of the immune system

Development of cytomegalovirus (CMV) immune recovery uveitis is associated with Th17 cell depletion and poor systemic CMV-specific T cell responses.

Backgroundthe immune reconstitution inflammatory syndromes (IRIS) are a spectrum of inflammatory conditions associated with opportunistic infections and occurring in approximately16% of human immunodeficiency type 1 (HIV-1)-infected patients given antiretroviral therapy. It has been proposed that these conditions are linked by a dysregulated immune system that is prone to exaggerated responses. However, immunologic studies have been limited by the availability of longitudinal samples from patients with IRIS and appropriate matched control subjects. Cytomegalovirus (CMV) immune recovery uveitis (IRU) is an IRIS occurring in up to 38% of patients with CMV retinitis. Although the pathologic immune responses occur in the eye, immune dysregulation that allows for development of pathologic responses is presumably caused by faulty systemic immune cell reconstitution.Methodswe examined CMV-specific T cell responses, regulatory T (T(reg)) cell function and polyclonal T cell responses, including IL-17 production, in 25 patients with CMV IRU and 49 immunorestored control subjects with CMV retinitis who did not develop IRU.Resultspatients with CMV IRU had poor CMV-specific CD4(+) T cell responses, as compared with control subjects, whereas CD8(+) T cell responses were comparable. Patients with CMV IRU were characterized by smaller numbers of circulating Th17 cells. Deficiency in anti-CMV responses was not associated with differences in T(reg) cell function.Conclusionsthe T(reg) cell compartment is intact in patients with CMV IRU, and these patients do not develop exaggerated systemic CMV-specific or polyclonal immune responses. Cases are instead characterized by more profound depletion of Th17 cells and poor antiviral immune responses. CMV IRU may be most likely to develop in persons experiencing the greatest degree of immune dysfunction before initiating highly active antiretroviral therapy

SapB and the rodlins are required for development of Streptomyces coelicolor in high osmolarity media

Streptomyces coelicolor produces spore-forming aerial hyphae after a period of vegetative growth. These aerial structures are decorated with a hydrophobic coating of rodlets consisting of chaplins and rodlins. Here, we show that rodlins and the surface-active peptide SapB are essential for development during growth in a medium with high osmolarity. To this end, both vegetative and aerial hyphae secrete SapB, whereas rodlins are only secreted by the spore-forming aerial hyphae.

Dicarbon­yl(η5-cyclo­penta­dien­yl)[2-(phenyl­sulfan­yl)eth­yl]iron(II)

The title compound, [Fe(C5H5)(C8H9S)(CO)2], is a three-legged piano-stool iron(II) complex that is characterized by a thio­ethyl-linked phenyl ring and a cyclo­penta­dienyl moiety that occupies the apical coordination site. The two aromatic rings are essentially planar with the same maximum deviation of 0.009 Å. The mean planes of the phenyl and cyclo­penta­dienyl rings bis­ect at an acute angle of 50.08°

Designing evaluation plans for health promotion mHealth interventions: a case study of the Milk Man mobile app

Evaluating complex health promotion interventions that use mobile apps requires comprehensive and adaptive evaluation plans. As mobile usage becomes increasingly sophisticated and personalised, broad evaluation plans are important in determining the impact and efficacy of a mobile health (mHealth) app. Evaluation should consider user feedback and outcome measures, as well as examine elements such as the robustness of the technology, the intervention principles and engagement strategies, and the interaction of the user with the technology. This paper introduces four mHealth evaluation models and tools and describes the evaluation plan that has been developed for Milk Man, a breastfeeding app targeting new and expectant fathers. Milk Man is a socially connected, gamified app that is being tested in a large Randomised Control Trial (RCT). While there is a need for mobile apps to be evaluated in adequately powered RCTs, trialling mobile apps over a long period of time presents challenges. Incorporating robust evaluation design will help ensure that technological performance, app intervention principles, as well as health and behavioural outcomes are measured. The detail and scope of the Milk Man app evaluation plan will ensure the findings add to the evidence base and have broad relevance to health promotion practitioners.So what? Evidence about the efficacy of mHealth interventions is an emerging area and appropriate evaluation skills are needed. This paper illustrates an evaluation planning approach for mHealth interventions that could be adapted for use by health promotion practitioners and researchers

Development of Cytomegalovirus (CMV) Immune Recovery Uveitis Is Associated with Th17 Cell Depletion and Poor Systemic CMV-Specific T Cell Responses

We tested whether impaired systemic immunoregulation and hyperactive immune responses are associated with an immune reconstitution inflammatory syndrome, CMV IRU. We found instead that T-regs in CMV IRU patients are functionally intact, while virus-specific immune responses and Th17 cells are compromise