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allied
academies
J u n e 2 8 - 2 9 , 2 0 1 8 | A m s t e r d a m , N e t h e r l a n d s
Joint Event on
OBESITY AND WEIGHT MANAGEMENT
VACCINES AND IMMUNOLOGY
&
International Conference on
International Conference on
Asian Journal of Biomedical and Pharmaceutical Sciences
|
Volume 8
ISSN:
2249-622X
Asian J Biomed Pharmaceut Sci 2018, Volume 8 | DOI: 10.4066/2249-622X-C1-003
THE HALLMARKS OF TUBERCULOSIS AND THEIR CLINICAL
SIGNIFICANCE
Zlatko Dembic
University of Oslo, Norway
Introduction:
Heritable susceptibility to tuberculosis (TB) is complex and polygenic in nature. Only five to 10 percent of humans
that meet the bacterium
Mycobacterium tuberculosis
(Mt) will manifest the disease, provided no acquired- or congenital
immunodeficiency were present. We still lack a viable explanation for the observed epidemiologic fact.
Background:
Activation of macrophages via pro-inflammatory cytokines IFN- and Interleukin (IL)-17 can kill intracellular bacteria
such as
Mt
. Instead, macrophages stimulated by the toll-like receptor (TLR)-10 agonists show an anti-inflammatory effect. The
TLR-10 acts by inhibiting the TLR-2 signaling from the cell membrane. The TLR-2 is the Mt-binding protein by which activated
macrophages can internalize (and kill) Mt. Inactivation of the TLR-2 protein might convey a risk for developing the disease. This
was supported by our finding that
TLR2
gene polymorphisms, which either inactivate the
TLR2
gene product or have a dominant-
negative role in TLR-2-signaling are associated with elevated risk for tuberculosis in the Croatian Caucasian population.
Findings:
The genome-wide study found that three single nucleotide polymorphisms (SNPs) within the HLA class II loci were
significantly associated with TB (Nat Gen, 2016) suggesting that adaptive immunity is of paramount importance for defense
against TB. In our studied population, an SNP in the
TLR10
gene was associated with risk for TB, analyzed by the dominant model
of inheritance, however, this was contrasted by the fact that SNPs in the
IL17A
and
F
genes were not.
Conclusion & Significance:
Studying genetic risk by association analyses or genome-wide screening led us propose that
clinical manifestation of TB is a state above certain risk-threshold. Threshold is reached by accumulation of seemingly minor
susceptibilities divided between the hallmarks of the disease (we suggest there are five hallmarks). The model suggests that every
human population has its own mosaic of genetic risks for TB.
zlatko.dembic@odont.uio.no