Galectin-9 signaling prolongs survival in murine lung-cancer by inducing macrophages to differentiate into plasmacytoid dendritic cell-like macrophages

Galectin-9 (Gal-9) expanded plasmacytoid dendritic cell-like macrophages (pDC-M phi s) in lung cancer-bearing mice and prolonged the survival. Gal-9 increased the frequency of CD11c(high) cells in M-CSF- but not GM-CSF-induced M phi s in vitro in a Tim-3 independent manner. CD11C(high) cells differentiated with M-CSF+Gal-9 expressed pDC-M phi markers, such as PDCA-1 and F4/80. These cells expressed high TLR7, TLR8 and TLR9, although they exhibited decreased IFN-alpha mRNA levels. LPS or LLC stimulation further elevated pDC-M phi markers, indicating that M-CSF+Gal-9-induced M phi s were pDC-M phi precursors. Moreover, LPS stimulation resulted in the increased IRF7 and E2-2 levels, suggesting that the pDC-M phi precursors matured into pDC-M phi s. These matured pDC-M phi s augmented NK cell-mediated cytotoxicity though they did not produce IFN-alpha upon TLR7 or TLR9 stimulation. The present results suggest that Gal-9 induces M phi s to differentiate to pDC-M phi s, and that this switch in differentiation favors the activation of NK cells that are able to prolong the survival of tumor-bearing mice. (C) 2011 Elsevier Inc. All rights reserved.