Accumulation of Myeloid-Derived Suppressor Cells in the Lungs during Pneumocystis Pneumonia

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of hematopoietic precursors with the ability to adversely affect host immunity. They have been shown to accumulate in pathological conditions, such as cancer and some microbial diseases. In the mouse and rat models of Pneumocystis pneumonia (PcP), we found a distinct population of cells with MDSC-like morphology in the bronchoalveolar lavage (BAL) fluid, constituting up to 50% of the total cells in BAL fluid. These cells were not seen in the BAL fluid from normal animals or from Pneumocystis-infected animals that had been successfully treated for PcP with a combination of trimethoprim and sulfamethoxazole. With flow cytometry, these cells were found to express the characteristic MDSC surface markers Gr-1 and CD11b in mice or CD11bc and His48 in rats. Using reverse transcription-PCR, we demonstrated that these cells produced high levels of arginase-1 and inducible nitric oxide synthase (iNOS) mRNA. These cells were shown to suppress CD4(+)T-cell proliferation in response to stimulation by anti-CD3 and anti-CD28 antibodies. Adoptive transfer of these cells to normal mice caused lung damage, as indicated by elevated levels of albumin and lactate dehydrogenase in the BAL fluid. These experiments provide evidence of the presence of MDSCs in the lungs during PcP. Further studies on the roles of MDSCs in PcP are warranted in order to develop treatment strategies which can reduce the number of MDSCs and the damage caused by these cells.