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Most infections with Mycobacterium tuberculosis (Mtb) manifest as a clinically asymptomatic, contained state, known as latent tuberculosis infection, that affects approximately one-quarter of the global population.sup.1. Although fewer than one in ten individuals eventually progress to active disease.sup.2, tuberculosis is a leading cause of death from infectious disease worldwide.sup.3. Despite intense efforts, immune factors that influence the infection outcomes remain poorly defined. Here we used integrated analyses of multiple cohorts to identify stage-specific host responses to Mtb infection. First, using high-dimensional mass cytometry analyses and functional assays of a cohort of South African adolescents, we show that latent tuberculosis is associated with enhanced cytotoxic responses, which are mostly mediated by CD16 (also known as Fc[gamma]RIIIa) and natural killer cells, and continuous inflammation coupled with immune deviations in both T and B cell compartments. Next, using cell-type deconvolution of transcriptomic data from several cohorts of different ages, genetic backgrounds, geographical locations and infection stages, we show that although deviations in peripheral B and T cell compartments generally start at latency, they are heterogeneous across cohorts. However, an increase in the abundance of circulating natural killer cells in tuberculosis latency, with a corresponding decrease during active disease and a return to baseline levels upon clinical cure are features that are common to all cohorts. Furthermore, by analysing three longitudinal cohorts, we find that changes in peripheral levels of natural killer cells can inform disease progression and treatment responses, and inversely correlate with the inflammatory state of the lungs of patients with active tuberculosis. Together, our findings offer crucial insights into the underlying pathophysiology of tuberculosis latency, and identify factors that may influence infection outcomes.Integrated analyses of multiple cohorts are used to obtain a better understanding of the immune state of latent infection with Mycobacterium tuberculosis, and factors that mediate and/or predict transitions from latent infection to active disease., Author(s): Roshni Roy Chowdhury [sup.1] [sup.2] , Francesco Vallania [sup.3] [sup.4] , Qiantian Yang [sup.5] , Cesar Joel Lopez Angel [sup.1] [sup.2] , Fatoumatta Darboe [sup.6] [sup.7] , Adam Penn-Nicholson [...]

During the first 5 years of life, children are especially vulnerable to infection-related morbidity and mortality. Conversely, the Hygiene Hypothesis suggests that a lack of exposure to infectious agents early in life could explain the increasing incidence of allergies and autoimmunity in high-income countries. Understanding these phenomena, however, is hampered by a lack of comprehensive, direct immune monitoring in children with differing degrees of microbial exposure. Using mass cytometry, we provide an in-depth profile of the peripheral blood mononuclear cells (PBMCs) of children in regions at the extremes of exposure: the San Francisco Bay Area, USA and an economically poor district of Dhaka, Bangladesh. Despite variability in clinical health, functional characteristics of PBMCs were similar in Bangladeshi and American children at 1 year of age. However, by 2–3 years of age, Bangladeshi children's immune cells often demonstrated altered activation and cytokine production profiles upon stimulation with PMA-ionomycin, with an overall immune trajectory more in line with American adults. Conversely, immune responses in children from the US remained steady. Using principal component analysis, donor location, ethnic background, and cytomegalovirus infection status were found to account for some of the variation identified among samples. Within Bangladeshi 1-year-olds, stunting (as measured by height-for-age z-scores) was found to be associated with IL-8 and TGFβ expression in PMA-ionomycin stimulated samples. Combined, these findings provide important insights into the immune systems of children in high vs. low microbial exposure environments and suggest an important role for IL-8 and TGFβ in mitigating the microbial challenges faced by the Bangladeshi children.

Abstract: For malaria transmission, Plasmodium parasites must develop in the mosquito vector. Oxidative stress in the insect midgut, triggered by environmental changes (e.g., pH and temperature), influences the cellular signaling [...]

This study investigates and compares the relative importance of Web module design dimensions and their attributes as perceived by student participants in a research study and those defined by a selected group of researchers in the literature. We aim to understand whether the dimensions of clarity, organization, structure, visual/aesthetical attractiveness, simplicity, and excitement defined by students agree with the definitions in the literature. Content analysis methodology was used to extract the common language between the two groups and the attributes that best describe each dimension. The results show both similarities and differences between the two groups. The results suggest that organization and structure are different design dimensions, as are simplicity and clarity. The studied dimensions showed the following order in decreasing importance: clarity, organization, simplicity, structure, visual/aesthetical attractiveness, and excitement. Further, the characteristics of "text" and how it is used in a Web module appear to be a design attribute that influences all the design dimensions. (Contains 2 figures and 7 tables.)