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Dioxin and Host Susceptibility to Infection
Vivek Mehta
Mentor: Sastry Gollapudi
Dioxin, an environmental pollutant, increases host susceptibility to infection, but little is known
about the mechanisms by which this occurs. Recent research has identified a family of molecules
known as the Toll-like receptors (TLR’s) that play a key role in pathogen recognition and initiation of
inflammatory and immune response. The purpose of this study was to determine the effect dioxin
might have on the expression of TLR’s and TLR signaling. A monocytic cell line (U937, ATCC) was
cultured with various concentrations of Dioxin (1 ng/ml, 10 ng/ml, 50 ng/ml, 100 ng/ml) for 2
weeks. Cells were stained phycoerythrin (PE) labeled monoclonal antibodies against TLR 2, TLR 4
and isotype control antibody. Dioxin treated and control cells were stimulated with lipopolysaccharde
(LPS, 10 ug/ml), an agent known to trigger cell activation via TLR 4. Control and activated cells were
permeabilized and stained with PE labeled anti-TNF- antibody. 10,000 stained cells were acquired
and analyzed by FACScan flow cytometer. TLR positive cells, TLR receptor density, as well as the
percentage of TNF- producing cells were determined using cell quest software program. Dioxin, in
a concentration-dependent manner, inhibited the expression of TLR 2 and TLR 4. Altered
expression of TLR 4 was associated with a decreased production of TNF- These data suggest that
dioxin may increase host susceptibility to infection by modulating TLR expression and TLR signaling.