Cutting edge: mast cells critically augment myeloid-derived suppressor cell activity.
Myeloid-derived suppressor cells (MDSCs) are primarily recognized for their immunosuppressive properties in malignant disease. However, their interaction with other innate immune cells and their regulation of immune responses, such as in parasitic infection, necessitate further characterization. We used our previously published mouse model of MDSC accumulation to examine the immunoregulatory role of MDSCs in B16 melanoma metastasis and Nippostrongylus brasiliensis infection. In this study, we demonstrate that the activity of MDSCs is dependent on the immune stimuli and subset induced. Monocytic MDSCs predictably suppressed antitumor immune responses but granulocytic MDSCs surprisingly enhanced the clearance of N. brasiliensis infection. Intriguingly, both results were dependent on MDSC interaction with mast cells (MCs), as demonstrated by adoptive-transfer studies in MC-deficient (Kit(Wsh)(/)(Wsh)) mice. These findings were further supported by ex vivo cocultures of MCs and MDSCs, indicating a synergistic increase in cytokine production. Thus, MCs can enhance both immunosuppressive and immunosupportive functions of MDSCs.
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Sheinei J
SJ
Saleem
Rebecca K
RK
Martin
Johanna K
JK
Morales
Jamie L
JL
Sturgill
David R
DR
Gibb
Laura
L
Graham
Harry D
HD
Bear
Masoud H
MH
Manjili
John J
JJ
Ryan
Daniel H
DH
Conrad
D000818:Animals; D018827:Carcinoma, Lewis Lung; D002450:Cell Communication / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D006098:Granulocytes / Q000276:immunology / Q000469:parasitology; D008407:Mast Cells / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D009559:Nippostrongylus / Q000276:immunology