In:
The Journal of Immunology, The American Association of Immunologists, Vol. 188, No. 1_Supplement ( 2012-05-01), p. 117.4-117.4
Abstract:
Chronic exposure to air pollution increases susceptibility to respiratory infections including tuberculosis in humans. We hypothesized that exposure to diesel exhaust particles (DEP), a major component of urban fine particulate matter, suppresses antimycobacterial human immune effector cell functions by modulating TLR-signaling pathways and NF-κB activation. To examine the effects of DEP on M.tb-induced host immunity, PBMC from 20 healthy persons [13 m, 7 f, mean age 33.5 years) were stimulated with DEP and M.tb or PPD (purified protein derivative). We show by TEM studies that both DEP and H37Ra, an avirulent laboratory strain of M.tb, were taken up by the same peripheral CD14+CD3- blood monocytes. M.tb and PPD-induced IFN-γ, TNF-α, IL-1β, and IL-6 production was reduced in a DEP dose-dependent manner. In contrast, the production of anti-inflammatory IL-10 remained unchanged. DEP stimulation prior to M.tb infection altered the expression of mRNAs encoding TLR 3, 4, 5, 7 and 10 and a subset of M.tb-induced host genes including the inhibition of many NF-κB and IRF pathway target genes. We propose that DEP down-regulate M.tb-induced host gene expression via MyD88-dependent (IL6, IL1A, PTGS2) and MyD88-independent (IFNA, IFNB) pathways. Pre-stimulation of PBMC with DEP suppressed the expression of proinflammatory mediators upon M.tb infection inducing a hypo-responsive cellular state. These findings provide possible mechanism by which air pollutants alter antimicrobial immunity.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.188.Supp.117.4
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2012
detail.hit.zdb_id:
1475085-5
