Cutting edge: mast cells critically augment myeloid-derived suppressor cell activity.
Sheinei J Saleem1, Rebecca K Martin, Johanna K Morales
1Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|June 19, 2012
Summary
Myeloid-derived suppressor cells (MDSCs) exhibit dual roles in immunity. Granulocytic MDSCs aid parasitic infection clearance, while monocytic MDSCs suppress anti-tumor responses, both influenced by mast cell interactions.
Area of Science:
- Immunology
- Cell Biology
- Parasitology
Background:
- Myeloid-derived suppressor cells (MDSCs) are known for immune suppression in cancer.
- Their roles in other immune responses, like parasitic infections, require more study.
- Understanding MDSC interactions with other immune cells is crucial.
Purpose of the Study:
- To investigate the immunoregulatory functions of MDSCs in B16 melanoma metastasis and Nippostrongylus brasiliensis infection.
- To explore the influence of different immune stimuli and MDSC subsets on immune responses.
- To elucidate the role of mast cells (MCs) in modulating MDSC activity.
Main Methods:
- Utilized a previously established mouse model of MDSC accumulation.
- Examined MDSC function in B16 melanoma metastasis and N. brasiliensis infection models.
- Conducted adoptive-transfer studies in mast cell-deficient mice (Kit(Wsh)(/)(Wsh)).
- Performed ex vivo co-cultures of mast cells and MDSCs.
Main Results:
- MDSC activity varied based on immune stimuli and induced subset.
- Monocytic MDSCs suppressed anti-tumor immunity.
- Granulocytic MDSCs enhanced clearance of N. brasiliensis infection.
- Both observed effects were dependent on MDSC-mast cell interactions.
- Co-cultures showed synergistic cytokine production between MDSCs and MCs.
Conclusions:
- Mast cells significantly enhance both the immunosuppressive and immunosupportive functions of MDSCs.
- MDSC functions are context-dependent and involve intricate crosstalk with other immune cells like mast cells.
- This study reveals a novel regulatory mechanism of MDSC activity with implications for cancer immunotherapy and infectious disease treatment.
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