Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages

This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments

Threat-sensitive anti-predator defence in precocial wader, the northern lapwing Vanellus vanellus

Birds exhibit various forms of anti-predator behaviours to avoid reproductive failure, with mobbing—observation, approach and usually harassment of a predator—being one of the most commonly observed. Here, we investigate patterns of temporal variation in the mobbing response exhibited by a precocial species, the northern lapwing (Vanellus vanellus). We test whether brood age and self-reliance, or the perceived risk posed by various predators, affect mobbing response of lapwings. We quantified aggressive interactions between lapwings and their natural avian predators and used generalized additive models to test how timing and predator species identity are related to the mobbing response of lapwings. Lapwings diversified mobbing response within the breeding season and depending on predator species. Raven Corvus corax, hooded crow Corvus cornix and harriers evoked the strongest response, while common buzzard Buteo buteo, white stork Ciconia ciconia, black-headed gull Chroicocephalus ridibundus and rook Corvus frugilegus were less frequently attacked. Lapwings increased their mobbing response against raven, common buzzard, white stork and rook throughout the breeding season, while defence against hooded crow, harriers and black-headed gull did not exhibit clear temporal patterns. Mobbing behaviour of lapwings apparently constitutes a flexible anti-predator strategy. The anti-predator response depends on predator species, which may suggest that lapwings distinguish between predator types and match mobbing response to the perceived hazard at different stages of the breeding cycle. We conclude that a single species may exhibit various patterns of temporal variation in anti-predator defence, which may correspond with various hypotheses derived from parental investment theory

More stories on Th17 cells

For more than two decades, immunologists have been using the so-called Th1/Th2 paradigm to explain most of the phenomena related to adaptive immunity. the Th1/Th2 paradigm implied the existence of two different, mutually regulated, CD4(+) T helper subsets: Th1 cells, driving cell-mediated immune responses involved in tissue damage and fighting infection against intracellular parasites; and Th2 cells that mediate IgE production and are particularly involved in eosinophilic inflammation, allergy and clearance of helminthic infections. A third member of the T helper set, IL-17-producing CD4(+) T cells, now called Th17 cells, was recently described as a distinct lineage that does not share developmental pathways with either Th1 or Th2 cells. the Th17 subset has been linked to autoimmune disorders, being able to produce IL-17, IL-17F and IL-21 among other inflammatory cytokines. Interestingly, it has been reported that there is not only a cross-regulation among Th1, Th2 and Th17 effector cells but there is also a dichotomy in the generation of Th17 and T regulatory cells. Therefore, Treg and Th17 effector cells arise in a mutually exclusive fashion, depending on whether they are activated in the presence of TGF-beta or TGF-beta plus inflammatory cytokines such as IL-6. This review will address the discovery of the Th17 cells, and recent progress on their development and regulation.Crohn's and Colitis Foundation of AmericaNIHLa Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USAUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilNIH: RO1 AI050265-06Web of Scienc

Control of CydB and GltA1 Expression by the SenX3 RegX3 Two Component Regulatory System of Mycobacterium tuberculosis

Two component regulatory systems are used widely by bacteria to coordinate changes in global gene expression profiles in response to environmental signals. The SenX3-RegX3 two component system of Mycobacterium tuberculosis has previously been shown to play a role in virulence and phosphate-responsive control of gene expression. We demonstrate that expression of SenX3-RegX3 is controlled in response to growth conditions, although the absolute changes are small. Global gene expression profiling of a RegX3 deletion strain and wild-type strain in different culture conditions (static, microaerobic, anaerobic), as well as in an over-expressing strain identified a number of genes with changed expression patterns. Among those were genes previously identified as differentially regulated in aerobic culture, including ald (encoding alanine dehydrogenase) cyd,encoding a subunit of the cytochrome D ubiquinol oxidase, and gltA1, encoding a citrate synthase. Promoter activity in the upstream regions of both cydB and gltA1 was altered in the RegX3 deletion strain. DNA-binding assays confirmed that RegX3 binds to the promoter regions of ald, cydB and gltA1 in a phosphorylation-dependent manner. Taken together these data suggest a direct role for the SenX-RegX3 system in modulating expression of aerobic respiration, in addition to its role during phosphate limitation

The Cost of Autism Spectrum Disorders

Objective: A diagnosis of an autism spectrum disorders is usually associated with substantial lifetime costs to an individual, their family and the community. However, there remains an elusive factor in any cost-benefit analysis of ASD diagnosis, namely the cost of not obtaining a diagnosis. Given the infeasibility of estimating the costs of a population that, by its nature, is inaccessible, the current study compares expenses between families whose children received a formal ASD diagnosis immediately upon suspecting developmental atypicality and seeking advice, with families that experienced a delay between first suspicion and formal diagnosis. Design: A register based questionnaire study covering all families with a child with ASD in Western Australia. Participants: Families with one or more children diagnosed with an ASD, totalling 521 children diagnosed with an ASD; 317 records were able to be included in the final analysis.Results: The median family cost of ASD was estimated to be AUD $34,900 per annum with almost 90$29,200) due to loss of income from employment. For each additional symptom reported, approximately $1,400 cost for the family per annum was added. While there was little direct influence on costs associated with a delay in the diagnosis, the delay was associated with a modest increase in the number of ASD symptoms, indirectly impacting the cost of ASD. Conclusions: A delay in diagnosis was associated with an indirect increased financial burden to families. Early and appropriate access to early intervention is known to improve a child's long-term outcomes and reduce lifetime costs to the individual, family and society. Consequently, a per symptom dollar value may assist in allocation of individualised funding amounts for interventions rather than a nominal amount allocated to all children below a certain age, regardless of symptom presentation, as is the case in Western Australia

Heritable symbionts in a world of varying temperature

Heritable microbes represent an important component of the biology, ecology and evolution of many plants, animals and fungi, acting as both parasites and partners. In this review, we examine how heritable symbiont–host interactions may alter host thermal tolerance, and how the dynamics of these interactions may more generally be altered by thermal environment. Obligate symbionts, those required by their host, are considered to represent a thermally sensitive weak point for their host, associated with accumulation of deleterious mutations. As such, these symbionts may represent an important determinant of host thermal envelope and spatial distribution. We then examine the varied relationship between thermal environment and the frequency of facultative symbionts that provide ecologically contingent benefits or act as parasites. We note that some facultative symbionts directly alter host thermotolerance. We outline how thermal environment will alter the benefits/costs of infection more widely, and additionally modulate vertical transmission efficiency. Multiple patterns are observed, with symbionts being cold sensitive in some species and heat sensitive in others, with varying and non-coincident thresholds at which phenotype and transmission are ablated. Nevertheless, it is clear that studies aiming to predict ecological and evolutionary dynamics of symbiont–host interactions need to examine the interaction across a range of thermal environments. Finally, we discuss the importance of thermal sensitivity in predicting the success/failure of symbionts to spread into novel species following natural/engineered introduction

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events

Mycobacterium tuberculosis acg Gene Is Required for Growth and Virulence In Vivo

Mycobacterium tuberculosis dosRS two-component regulatory system controls transcription of approximately 50 genes including hspX, acg and Rv2030c, in response to hypoxia and nitric oxide conditions and within macrophages and mice. The hspX lies between acg and Rv2030c. However, the functions of the dosR regulated genes in vitro and in vivo are largely unknown. Previously, we demonstrated that deletion of hspX gene produced a mutant which grew faster in macrophages and in mice. In this study, we attempted to determine the functions of acg and Rv2030c by gene inactivation. We demonstrate that Rv2030c is dispensable for virulence and growth. However, deletion of acg produced a mutant which is attenuated in both resting and activated macrophages and in acute and persistent murine infection models. Surprisingly, deletion of acg did not compromise the viability of the mutant to nitrosative and oxidative stresses in vitro and in vivo. In addition, when the WT and the acg mutants were treated with antibiotics such as the prodrugs nitrofurantoin and nitrofuran, the acg mutant became more sensitive than the WT strain to these drugs. This suggests that Acg may not function as a nitroreductase. These data indicate that acg encodes an essential virulence factor for M. tuberculosis and enables it to grow and survive in macrophages and in mouse organs