Characterization of myeloid suppressor cell activity in experimental leishmaniasis
Final Report Abstract
It is obvious that myeloid cell subsets are crucial for the modulation of the adaptive and innate immune response against intracellular pathogens such as Leishmania major parasites. Based on the overlapping expression of molecules that were commonly used to classify myeloid cells, it becomes difficult to denominate those cell types precisely. Of note, most of these markers used for myeloid cell identification are expressed on a broad range of myeloid cells, and should therefore be handled with care if used for sub typing of myeloid cells. In my point of view it cannot be excluded that the subsets that were denominated as myeloid suppressor cells (MDSCs) might not be classical "subsets" but rather represent myeloid cells in a transient maturation stage expressing different genes, in response to the surrounding environment. Nevertheless we started to characterize the function of MDSCs subsets in experimental leishmaniasis. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of CD11b+ cells. According to the surface molecules Ly6G and Ly6C (where Ly6G and Ly6C are lymphocyte antigen 6, locus G and C, respectively), MDSCs are further divided into monocytic (Mo-MDSCs, CD11b+ /Ly6Chigh/Ly6G) and polymorphonucleated suppressor cells (PMN-MDSCs, CD11b+ /Ly6C'nt/Ly6G+). Most published manuscripts focus on the suppressive role of MDSCs in cancer, whereas their impact on adaptive immunity against obligatory intracellular parasites is not well understood. Furthermore, it is not clear how the genetic background of mice influences MDSC functionality. Therefore, we implemented an experimental model of leishmaniasis, and analyzed MDSC maturation and the impact of MDSCs on the parasite-specific T-cell responses in resistant C57BL/6 and susceptible BALB/c mice. This experimental setup demonstrated the impaired ability of BALB/c mice to produce Mo-MDSCs when compared with C57BL/6 mice. This phenotype is detectable after subcutaneous infection with parasites and is specifically represented by a reduced accumulation of Mo-MDSCs at the site of infection in BALB/c mice. Moreover, infected C57BL/6-derived MDSCs were able to suppress Leishmania-specific CD4+-cell proliferation, whereas BALB/c-derived MDSCs harbouring parasites lost this suppressive function. In conclusion, we demonstrate that (i) genetic background defines MDSC differentiation; and (ii) Leishmania major parasites are able to modulate the suppressive effect of MDSCs in a strain-dependent manner.
Publications
-
In
the
experimental
model
of
leishmaniasis
myeloid‐derived
suppressor
cell
functions
and
interaction
with
parasites
differs
between
C57BL/6
and
BALB/c.
Biomedical
Symposium
for
Graduate
Students,
4.‐5.
Nov.
2011,
Regen,
Germany.
Schmid M., Nicole Z., Männel D.N. and Ritter U.
-
The
homing
of
myeloid‐derived
suppressor
cells
and
interaction
with
leucocytes
differs
between
C57BL/6
and
BALB/c
after
infection
with
Leishmania
major.
2011.
41th
Annual
Meeting
of
the
German
Society
of
Immunology.
Riccione,
Italy.
Schmid M., Nicole Z., Männel D.N. and Ritter U
- Characteristics
of
“Tip‐DCs
and
MDSCs”
and
their
potential
role
in
leishmaniasis.
Frontiers
in
Microbiology.
2012
3:
74
Schmid M., Wege A‐K. and Ritter U.
(See online at https://doi.org/10.3389/fmicb.2012.00074) - Characterization
of
myeloid
suppressor
cell
activity
in
experimental
leishmaniasis.
2012.
Symposium
“Infection
and
immune
defence”,
Rothenfels.
Würzburg,
Germany.
Schmid M.
- In
the
experimental
model
of
leishmaniasis
myeloid‐derived
suppressor
cell
functions
and
interaction
with
parasites
differs
between
C57BL/6
and
BALB/c.
Biomedical
Symposium
for
Graduate
Students,
9./10.
Nov.
2012,
Regen,
Germany
Schmid M.
- In
the
experimental
model
of
leishmaniasis
myeloid‐derived
suppressor
cell
functions
and
interaction
with
parasites
differs
between
C57BL/6
and
BALB/c.
Biomedical
Symposium
for
Graduate
Students,
9./10.
Nov.
2012,
Regen,
Germany.
Schmid M., Nicole Z., and Ritter U.
- Myeloid
cells:
Modulators
of
adaptive
immunity.
University
Hospital
Eppendorf,
Hamburg,
Germany
(Liver
SFB
841).
Ritter U.
- Langerhans
cells
promote
early
germinal
center
formation
in
response
to
Leishmania‐derived
cutaneous
antigens.
European
Journal
of
Immunology.
2014
Oct;44(10):2955‐67.
Zimara N., Florian C., Schmid M., Malissen B., Kissenpfennig A., Männel DN., Edinger M., Hutchinson J.A., Hoffmann P., Ritter U.
(See online at https://doi.org/10.1002/eji.201344263) - Myeloid‐derived
suppressor
cell
functiontionality
and
interaction
with
Leishmania
parasites
differ
in
C57BL/6
and
BALB/c
mice.
European
Journal
of
Immunology.
2014
Nov;44(11):3295‐306
Schmid M., Zimara N., Wege A.‐K., Ritter U.
(See online at https://doi.org/10.1002/eji.201344335) - An emerging approach for parallel quantification of intracellular protozoan parasites and host cell characterization using TissueFAXS cytometry. PLoS ONE 10(10): e0139866, 2015
Schmid M, Dufner B, Dürk J, Bedal K, Stricker K, Prokoph LA, et al.
(See online at https://doi.org/10.1371/journal.pone.0139866)
