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Myeloid‐derived suppressor cell functionality and interaction with Leishmania major parasites differ in C57BL/6 and BALB/c mice
Author(s) -
Schmid Maximilian,
Zimara Nicole,
Wege Anja Kathrin,
Ritter Uwe
Publication year - 2014
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201344335
Subject(s) - biology , balb/c , c57bl/6 , myeloid derived suppressor cell , leishmania major , leishmania , suppressor , leishmaniasis , myeloid , immunology , microbiology and biotechnology , parasite hosting , genetics , immune system , gene , world wide web , computer science
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 + /Ly6C high /Ly6G − ) and polymorphonucleated suppressor cells (PMN‐MDSCs, CD11b + /Ly6C int /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 + T‐cell proliferation, whereas BALB/c‐derived MDSCs harboring 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.