Association of household air pollution with cellular and humoral immune responses among women in rural Bangladesh.

Household air pollution (HAP) arising from combustion of biomass fuel (BMF) is a leading cause of morbidity and mortality in low-income countries. Air pollution may stimulate pro-inflammatory responses by activating diverse immune cells and cyto/chemokine expression, thereby contributing to diseases. We aimed to study cellular immune responses among women chronically exposed to HAP through use of BMF for domestic cooking. Among 200 healthy, non-smoking women in rural Bangladesh, we assessed exposure to HAP by measuring particulate matter 2.5 (PM2.5), black carbon (BC) and carbon monoxide (CO), through use of personal monitors RTI MicroPEM™ and Lascar CO logger respectively, for 48 h. Blood samples were collected following HAP exposure assessment and were analyzed for immunoprofiling by flow cytometry, plasma IgE by immunoassay analyzer and cyto/chemokine response from monocyte-derived-macrophages (MDM) and -dendritic cells (MDDC) by multiplex immunoassay. In multivariate linear regression model, a doubling of PM2.5 was associated with small increments in immature/early B cells (CD19+CD38+) and plasmablasts (CD19+CD38+CD27+). In contrast, a doubling of CO was associated with 1.20% reduction in CD19+ B lymphocytes (95% confidence interval (CI) = -2.36, -0.01). A doubling of PM2.5 and BC each was associated with 3.12% (95%CI = -5.85, -0.38) and 4.07% (95%CI = -7.96, -0.17) decrements in memory B cells (CD19+CD27+), respectively. Exposure to CO was associated with increased plasma IgE levels (beta(ß) = 240.4, 95%CI = 3.06, 477.8). PM2.5 and CO exposure was associated with increased MDM production of CXCL10 (ß = 12287, 95%CI = 1038, 23536) and CCL5 (ß = 835.7, 95%CI = 95.5, 1576), respectively. Conversely, BC exposure was associated with reduction in MDDC-produced CCL5 (ß = -3583, 95%CI = -6358, -807.8) and TNF-α (ß = -15521, 95%CI = -28968, -2074). Our findings suggest that chronic HAP exposure through BMF use adversely affects proportions of B lymphocytes, particularly memory B cells, plasma IgE levels and functions of antigen presenting cells in rural women.

Immune responses in the treatment of drug-sensitive pulmonary tuberculosis with phenylbutyrate and vitamin D3 as host directed therapy.

BACKGROUND: We have previously shown that 8 weeks' treatment with phenylbutyrate (PBA) (500mgx2/day) with or without vitamin D3 (vitD3) (5000 IU/day) as host-directed therapy (HDT) accelerated clinical recovery, sputum culture conversion and increased expression of cathelicidin LL-37 by immune cells in a randomized, placebo-controlled trial in adults with pulmonary tuberculosis (TB). In this study we further aimed to examine whether HDT with PBA and vitD3 promoted clinically beneficial immunomodulation to improve treatment outcomes in TB patients. METHODS: Cytokine concentration was measured in supernatants of peripheral blood mononuclear cells (PBMC) from patients (n = 31/group). Endoplasmic reticulum stress-related genes (GADD34 and XBP1spl) and human beta-defensin-1 (HBD1) gene expression were studied in monocyte-derived-macrophages (MDM) (n = 18/group) from PBMC of patients. Autophagy in MDM (n = 6/group) was evaluated using LC3 expression by confocal microscopy. RESULTS: A significant decline in the concentration of cytokines/chemokines was noted from week 0 to 8 in the PBA-group [TNF-α (ß = - 0.34, 95% CI = - 0.68, - 0.003; p = 0.04), CCL11 (ß = - 0.19, 95% CI = - 0.36, - 0.03; p = 0.02) and CCL5 (ß = - 0.08, 95% CI = - 0.16, 0.002; p = 0.05)] and vitD3-group [(CCL11 (ß = - 0.17, 95% CI = - 0.34, - 0.001; p = 0.04), CXCL10 (ß = - 0.38, 95% CI = - 0.77, 0.003; p = 0.05) and PDGF-ß (ß = - 0.16, 95% CI = - 0.31, 0.002; p = 0.05)] compared to placebo. Both PBA- and vitD3-groups showed a decline in XBP1spl mRNA on week 8 (p < 0.03). All treatment groups demonstrated increased LC3 expression in MDM compared to placebo over time (p < 0.037). CONCLUSION: The use of PBA and vitD3 as adjunct therapy to standard TB treatment promoted favorable immunomodulation to improve treatment outcomes. TRIALS REGISTRATION: This trial was retrospectively registered in clinicaltrials.gov, under identifier NCT01580007 .