| kathleen 2005-09-28, 9:03 am |
| If they hadn't insisted people with seronegative Lyme were crazy and
not sick, we would have discovered things like why the tuberculosis
vaccines failed, oh, maybe 20 yars ago.
If they hadn't blown off the adverse LymeRIX events patients, they
would have made some real medical advances 8-10 years previous to this:
J Immunol. 2001 Jul 15;167(2):910-8.
Toll-like receptor 2-dependent inhibition of macrophage class II MHC
expression and antigen processing by 19-kDa lipoprotein of
Mycobacterium tuberculosis.
Noss EH, Pai RK, Sellati TJ, Radolf JD, Belisle J, Golenbock DT, Boom
WH, Harding CV.
Department of Pathology, Case Western Reserve university and University
Hospitals of Cleveland, Cleveland, OH 44106, USA.
Mycobacterium tuberculosis (MTB) induces vigorous immune responses, yet
persists inside macrophages, evading host immunity. MTB bacilli or
lysate was found to inhibit macrophage expression of class II MHC
(MHC-II) molecules and MHC-II Ag processing. This report characterizes
and identifies a specific component of MTB that mediates these
inhibitory effects. The inhibitor was extracted from MTB lysate with
Triton X-114, isolated by gel electroelution, and identified with Abs
to be MTB 19-kDa lipoprotein. Electroelution- or
immunoaffinity-purified MTB 19-kDa lipoprotein inhibited MHC-II
expression and processing of both soluble Ags and Ag 85B from intact
MTB bacilli. Inhibition of MHC-II Ag processing by either MTB bacilli
or purified MTB 19-kDa lipoprotein was dependent on Toll-like receptor
(TLR) 2 and independent of TLR 4. Synthetic analogs of lipopeptides
from Treponema pallidum also inhibited Ag processing. Despite the
ability of MTB 19-kDa lipoprotein to activate microbicidal and innate
immune functions early in infection, TLR 2-dependent inhibition of
MHC-II expression and Ag processing by MTB 19-kDa lipoprotein during
later phases of macrophage infection may prevent presentation of MTB
Ags and decrease recognition by T cells. This mechanism may allow
intracellular MTB to evade immune surveillance and maintain chronic
infection.
PMID: 11441098 [PubMed - indexed for MEDLINE]
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