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Abstract: In this study, we have compared the immunological responses associated with early pulmonary mycobacterial infection in two mouse strains, BALB/c and C57BL/6 known to exhibit distinct differences in susceptibility to infection with several pathogens. We infected mice via the intranasal route. We have demonstrated that BALB/c was less able to control mycobacterial growth in the lungs during the early phase of pulmonary infection. Our results showed that during the early phase (day 3 to week 1), BALB/c mice exhibited a delay in the production of TNF and IFN-γ in the lungs compared to C57BL/6 mice. Levels of IL-12 and soluble TNF receptors (sTNFR) were comparable between the mouse strains. The cellular subset distribution in these mice before and after infection showed a higher increase in CD11b+ cells in the lungs of C57BL/6, compared to BALB/c as early as day 3 postinfection. At early time points, higher levels of monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein 1 (MIP)-α were detected in C57BL/6 than BALB/c mice. In vitro, BCG-infected bone marrow derived macrophages (BMM) from both mouse strains displayed similar capacities to either phagocytose bacteria or produce soluble mediators such as TNF, IL-12 and nitric oxide (NO). Although IFN-γ stimulation of infected BMM in both mouse strains resulted in the induction of antimycobacterial activity, BALB/c mice had a reduced capacity to kill ingested bacteria. The above observations indicate that the chain of early, possibly innate immunological events occurring during pulmonary mycobacterial infection may directly impact on increased susceptibility or resistance to infection. [Copyright &y& Elsevier]

Summary Autophagy, a homeostatic process whereby eukaryotic cells target cytoplasmic cargo for degradation, plays a broad role in health and disease states. Here we screened the TRIM family for roles in autophagy and found that half of TRIMs modulated autophagy. In mechanistic studies, we show that TRIMs associate with autophagy factors and act as platforms assembling ULK1 and Beclin 1 in their activated states. Furthermore, TRIM5α acts as a selective autophagy receptor. Based on direct sequence-specific recognition, TRIM5α delivered its cognate cytosolic target, a viral capsid protein, for autophagic degradation. Thus, our study establishes that TRIMs can function both as regulators of autophagy and as autophagic cargo receptors, and reveals a basis for selective autophagy in mammalian cells. [ABSTRACT FROM AUTHOR]

Highlights: [•] Autophagy is involved in control of Mycobacterium tuberculosis. [•] Autophagy can directly kill M. tuberculosis by a variety of mechanisms. [•] Autophagy can also modulate systemic immune responses in vivo during M. tuberculosis infection. [•] There are genetic links between autophagy and M. tuberculosis susceptibility in humans. [ABSTRACT FROM AUTHOR]

There is growing evidence that e-waste recyclers may be exposed to potentially high levels of metals though associations between such exposures and specific work activities is not well established. In addition, studies have focused on metals traditionally biomonitored and there is no data on the exposure of recyclers to elements increasingly being used in new technologies. In the current study, levels of metals were measured in blood and urine of e-waste recyclers at Agbogbloshie (Ghana) and a control group. Blood and urine samples (from 100 e-waste recyclers and 51 controls) were analyzed for 17 elements (Ag, As, Ba, Cd, Ce, Cr, Eu, La, Mn, Nd, Ni, Pb, Rb, Sr, Tb, Tl, Y) using the ICP-MS. Most e-waste recyclers reported performing at least 4 different tasks in decreasing order as e-waste dismantling (54%), trading/selling of e-waste (45%), burning wires only (40%), and collecting wires after burning (34%). Mean levels of blood Pb, Sr, Tl, and urinary Pb, Eu, La, Tb, and Tl were significantly higher in recyclers versus controls. In general, the collectors and sorters tended to have higher elemental levels than other work groups. Blood Pb levels (mean 92.4 μg/L) exceeded the U.S. CDC reference level in 84% of the e-waste recyclers. Likewise, blood Cd, Mn, and urinary As levels in recyclers and controls were higher than in reference populations elsewhere. E-waste recyclers are exposed to metals traditionally studied (e.g., Pb, Cd, As) and several other technology-critical and rare earth elements which previously have not been characterized through human biomonitoring. • e-waste workers are exposed to potentially high levels of diverse metals. • Biomonitoring of technology critical and rare earth elements seldom done. • Blood Pb, Sr, Tl and urinary Pb, Eu, La, Tb, and Tl higher in workers vs. controls. • Exposures linked to different e-waste work practices. [ABSTRACT FROM AUTHOR]

[Display omitted] • PM 2.5 and polycyclic aromatic hydrocarbons (PAHs) were monitored at an e-waste site. • PM and PAH concentrations in personal air were nearly double levels at fixed sites. • Workers performing burning and dismantling tasks had the highest exposures. • Both PM and PAH levels exceeded standards or risk-based guidelines. • Pollutant emissions at informal e-waste sites affects nearby communities. Electronic waste (e-waste) disposal and recycling activities such as burning and smelting can emit particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), and other pollutants that expose workers and nearby communities. At informal e-waste recycling facilities, both emission controls and protective measures for workers are absent. This study characterizes personal exposures (breathing zone) of PM and PAHs of e-waste workers at the large Agbogbloshie e-waste site in Accra, Ghana. We collected gravimetric and optical measurements of PM 2.5 and PM 10 using shift samples for workers and for an age- and gender-matched reference population. PM 2.5 filters were analyzed for 26 PAHs using gas chromatography/mass spectroscopy. Among e-waste workers, PM 2.5 and PM 10 concentrations were 99 ± 56 and 218 ± 158 µg/m3 (median ± interquartile range, optical measurements), respectively; these levels were 78 and 57% higher, respectively, than levels measured at a fixed site that was centrally located at the waste site. In the reference community, breathing zone PM 2.5 and PM 10 levels were lower, 49 ± 20 and 131 ± 108 µg/m3, respectively, and the fraction of coarse PM was larger. We detected all 26 target PAHs, of which naphthalene and phenanthrene were the most abundant. PAH concentrations were weakly correlated to PM levels, but PAH abundances, representing the fraction of PAH mass to the total PM 2.5 mass collected, were strongly and inversely correlated to PM levels, suggesting multiple and different sources of PAHs and PM that affected exposures. Both PM and PAH levels were elevated for workers performing burning and dismantling, and both exceeded standards or risk-based guidelines, e.g., lifetime excess cancer risks for several PAHs were in the 10−4 to 10−6 range, indicating the need to reduce emissions as well as provide respiratory protection. The study emphasizes the importance of using personal and shift samples to accurately characterize worker exposure. [ABSTRACT FROM AUTHOR]