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Characterization of myeloid suppressor cell activity in experimental leishmaniasis

Subject Area Immunology
Term from 2010 to 2014
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 188763720
 
Final Report Year 2015

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)
 
 

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