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J Parasit Dis Diagn Ther 2017 | Volume 2 Issue 4
International Conference on
Zoology, Microbiology & Medical Parasitology
October 30-November 01, 2017 | Chicago, USA
Thalidomide affects macrophage activation and Leshmania
Z Zhanzak
1
and
Y.Goto
2
1
Nazarbayev University, Kazakhistan
2
University of Tokyo, Kazakhistan
Keywords:
Leishmaniasis, thalidomide, macrophage
activation, cytokines
Introduction:
Leishmania parasites are the causative agents
of LEISHMANIASIS, group of vector-borne parasitic diseases
endemic worldwide. Once inoculated into the organism,
Leishmania parasites are rapidly uptaken by macrophages.
Macrophages areprimary resident cells for their proliferation:
they can either phagocyte or allow parasite growth. That is
why proper activation of macrophages is crucial in disease
fate. Macrophage activation is divided into two classes:
classical (M1) and alternative (M2) that induce parasite
killing and its survival, respectively. Classical activation
is mediated by pro-inflammatory cytokines which cause
macrophages to produce toxic molecules to kill intracellular
parasites. In contrast, alternative activation is induced by
anti-inflammatory cytokines that lead to parasite survival in
infected cells. Thalidomide is reported to stimulate immune
response and enhance cellular phagocytotic activity by
selectively inhibiting M2 pathway. Here, thalidomide was
examined as potential drug to have suppressive effect
on intracellular replication of L.major within infected
macrophages in-vitro.
Methods:
To observe macrophage activation, Raw264.7 cells
were cultured. After 24hr incubation of cells in 370
0
C, 5% CO
2
incubator, thalidomide treatment of different concentration
was done. Supernatant and pellet were collected for ELISA,
RT-PCR, qPCR and WB tests. To observe pathogen survival,
Raw 264.7 cells were cultured in chamber slides and infected
with L. major at 1:10 ratio. After 24hr incubation, thalidomide
treatment was done. Giemsa staining was applied to slides
and intracellular amastigote forms of L.major were counted.
Results:
In this study thalidomide’s effect on proper
macrophage activation and parasite survival was analyzed.
It was found that thalidomide can a) up-regulate pro-
inflammatory M1 macrophages (IFN-γ, TNF-α, iNOS); b)
down-regulate anti-inflammatory M2 macrophages (IL-
10 and Arg-1); c) decrease intracellular amastigotes of L.
major. Thalidomide shows inhibitory effect on alternative
activation of macrophages and induces M1 polarization
of macrophages, thus making them resistant to L. major
infection.
Conclusion:
Results highlight thalidomide’s potential
contribution to a new drug development towards
Leishmaniasis in the future.
Speaker Biography
Z Zhanzak is an undergraduate student in School of Science and Technology, Nazarbayev
University,Kazakhistan.
e:
zhuldyZ
Zhanzak@nu.edu.kz