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      Season and size of urban particulate matter differentially affect cytotoxicity and human immune responses to Mycobacterium tuberculosis

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          Abstract

          Exposure to air pollution particulate matter (PM) and tuberculosis (TB) are two of the leading global public health challenges affecting low and middle income countries. An estimated 4.26 million premature deaths are attributable to household air pollution and an additional 4.1 million to outdoor air pollution annually. Mycobacterium tuberculosis ( M. tb) infects a large proportion of the world’s population with the risk for TB development increasing during immunosuppressing conditions. There is strong evidence that such immunosuppressive conditions develop during household air pollution exposure, which increases rates of TB development. Exposure to urban air pollution has been shown to alter the outcome of TB therapy. Here we examined whether in vitro exposure to urban air pollution PM alters human immune responses to M. tb. PM 2.5 and PM 10 (aerodynamic diameters <2.5μm, <10μm) were collected monthly from rainy, cold-dry and warm-dry seasons in Iztapalapa, a highly populated TB-endemic municipality of Mexico City with elevated outdoor air pollution levels. We evaluated the effects of seasonality and size of PM on cytotoxicity and antimycobacterial host immunity in human peripheral blood mononuclear cells (PBMC) from interferon gamma (IFN-γ) release assay (IGRA)+ and IGRA- healthy study subjects. PM 10 from cold-dry and warm-dry seasons induced the highest cytotoxicity in PBMC. With the exception of PM 2.5 from the cold-dry season, pre-exposure to all seasonal PM reduced M. tb phagocytosis by PBMC. Furthermore, M. tb-induced IFN-γ production was suppressed in PM 2.5 and PM 10-pre-exposed PBMC from IGRA+ subjects. This observation coincides with the reduced expression of M. tb-induced T-bet, a transcription factor regulating IFN-γ expression in T cells. Pre-exposure to PM 10 compared to PM 2.5 led to greater loss of M. tb growth control. Exposure to PM 2.5 and PM 10 collected in different seasons differentially impairs M. tb-induced human host immunity, suggesting biological mechanisms underlying altered M. tb infection and TB treatment outcomes during air pollution exposures.

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          Most cited references41

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          The health effects of ambient PM2.5 and potential mechanisms

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            The Effect of Fine and Coarse Particulate Air Pollution on Mortality: A National Analysis

            Background Although many studies have examined the effects of air pollution on mortality, data limitations have resulted in fewer studies of both particulate matter with an aerodynamic diameter of ≤ 2.5 μm (PM2.5; fine particles) and of coarse particles (particles with an aerodynamic diameter > 2.5 and < 10 μm; PM coarse). We conducted a national, multicity time-series study of the acute effect of PM2.5 and PM coarse on the increased risk of death for all causes, cardiovascular disease (CVD), myocardial infarction (MI), stroke, and respiratory mortality for the years 1999–2005. Method We applied a city- and season-specific Poisson regression in 112 U.S. cities to examine the association of mean (day of death and previous day) PM2.5 and PM coarse with daily deaths. We combined the city-specific estimates using a random effects approach, in total, by season and by region. Results We found a 0.98% increase [95% confidence interval (CI), 0.75–1.22] in total mortality, a 0.85% increase (95% CI, 0.46–1.24) in CVD, a 1.18% increase (95% CI, 0.48–1.89) in MI, a 1.78% increase (95% CI, 0.96–2.62) in stroke, and a 1.68% increase (95% CI, 1.04–2.33) in respiratory deaths for a 10-μg/m3 increase in 2-day averaged PM2.5. The effects were higher in spring. For PM coarse, we found significant but smaller increases for all causes analyzed. Conclusions We conclude that our analysis showed an increased risk of mortality for all and specific causes associated with PM2.5, and the risks are higher than what was previously observed for PM10. In addition, coarse particles are also associated with more deaths.
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              IL-1β promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation.

              In vivo control of Mycobacterium tuberculosis reflects the balance between host immunity and bacterial evasion strategies. Effector Th1 cells that mediate protective immunity by depriving the bacterium of its intracellular niche are regulated to prevent overexuberant inflammation. One key immunoregulatory molecule is Tim3. Although Tim3 is generally recognized to downregulate Th1 responses, we recently described that its interaction with Galectin-9 expressed by M. tuberculosis-infected macrophages stimulates IL-1β secretion, which is essential for survival in the mouse model. Why IL-1β is required for host resistance to M. tuberculosis infection is unknown. In this article, we show that IL-1β directly kills M. tuberculosis in murine and human macrophages and does so through the recruitment of other antimicrobial effector molecules. IL-1β directly augments TNF signaling in macrophages through the upregulation of TNF secretion and TNFR1 cell surface expression, and results in activation of caspase-3. Thus, IL-1β and downstream TNF production lead to caspase-dependent restriction of intracellular M. tuberculosis growth.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Investigation
                Role: Data curationRole: Investigation
                Role: Data curationRole: Investigation
                Role: Formal analysisRole: Validation
                Role: ConceptualizationRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Writing – review & editing
                Role: Data curationRole: Formal analysis
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                11 July 2019
                2019
                : 14
                : 7
                : e0219122
                Affiliations
                [1 ] Department of Environmental and Occupational Health, Rutgers University School of Public Health, Piscataway, NJ, United States of America
                [2 ] Department of Microbiology, Instituto Nacional de Enfermedades Respiratorias, México City, México
                [3 ] Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
                [4 ] Duke Global Health Institute and Nicholas School of the Environment, Duke University, Durham, NC, United States of America
                [5 ] Division of Atmospheric Sciences, Desert Research Institute, Reno, NV, United States of America
                [6 ] Department of Biostatistics, Rutgers University School of Public Health, Piscataway, NJ, United States of America
                [7 ] Department of Urban-Global Public Health, Rutgers University School of Public Health, Newark, NJ, United States of America
                University of British Columbia, CANADA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                [¤]

                Current address: National Council of Science and Technology (CONACyT), Catedras-CONACyT-University Autonomous of Zacatecas, Zacatecas. Mexico.

                Author information
                http://orcid.org/0000-0002-0227-0122
                http://orcid.org/0000-0001-8287-7102
                http://orcid.org/0000-0001-5836-0699
                Article
                PONE-D-18-25717
                10.1371/journal.pone.0219122
                6622489
                31295271
                ad04b5a1-3687-4917-bb96-9ccf0202b094
                © 2019 Sarkar et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 1 September 2018
                : 17 June 2019
                Page count
                Figures: 7, Tables: 4, Pages: 20
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000066, National Institute of Environmental Health Sciences;
                Award ID: R01ES020382
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000066, National Institute of Environmental Health Sciences;
                Award ID: P30 ES005022
                Funded by: funder-id http://dx.doi.org/10.13039/100000066, National Institute of Environmental Health Sciences;
                Award ID: 3R01ES020382-05S1
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000139, U.S. Environmental Protection Agency;
                Award ID: FP-91782501-0
                Award Recipient :
                This work was supported by: S.S. (last), Grant R01ES020382, National Institute of Environmental Health Sciences, https://www.niehs.nih.gov/; S.S. (last), Grant P30 ES005022, National Institute of Environmental Health Sciences, https://www.niehs.nih.gov/; O.A.I., Grant 3R01ES020382-05S1, National Institute of Environmental Health Sciences, https://www.niehs.nih.gov/; O.A.I., EPA Star Award FP-91782501-0, United States Environmental Protection Agency, https://www.epa.gov/research-fellowships.
                Categories
                Research Article
                Ecology and Environmental Sciences
                Pollution
                Air Pollution
                Biology and Life Sciences
                Toxicology
                Cytotoxicity
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Toxicology
                Cytotoxicity
                Earth Sciences
                Seasons
                Biology and Life Sciences
                Developmental Biology
                Morphogenesis
                Growth Control
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Tuberculosis
                Medicine and Health Sciences
                Tropical Diseases
                Tuberculosis
                Biology and Life Sciences
                Immunology
                Immune Response
                Medicine and Health Sciences
                Immunology
                Immune Response
                Biology and Life Sciences
                Cell Biology
                Cell Processes
                Phagocytosis
                Medicine and Health Sciences
                Pulmonology
                Respiratory Infections
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

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