Colony-stimulating factors activate human macrophages to inhibit intracellular growth of Histoplasma capsulatum yeasts

Abstract

Recombinant cytokines and colony-stimulating factors (CSFs) were tested for their abilities to activate human monocytes/macrophages (Mφ) to inhibit the intracellular growth of or kill Histoplasma capsulatum yeasts. None of the cytokines or CSFs or combinations of cytokines and CSFs activated Mφ fungistatic activity when they were added to Mφ monolayers concurrently with yeasts. In contrast, culture of monocytes for 7 days in the presence of interleukin 3, granulocyte-Mφ CSF, or Mφ CSF stimulated Mφ fungistatic (but not fungicidal) activity against H. capsulatum yeasts in a concentration-dependent manner. Optimal activation of Mφ by CSFs required 5 days of coculture, and the cultures had to be initiated with freshly isolated peripheral blood monocytes. Culture of monocytes with combinations of CSFs or addition of CSFs during the 24 h of coculture with the yeasts did not further enhance Mφ fungistatic activity for H. capsulatum. Addition of gamma interferon or tumor necrosis factor alpha to CSF-activated Mφ also did not enhance Mφ fungistatic activity. These results suggest that interleukin 3, granulocyte-Mφ CSF, and Mφ CSF may play a role in the cell-mediated immune response to H. capsulatum by enhancing monocyte/Mφ fungistatic activity.