A sub-inhibitory concentration of amphotericin B enhances candidastatic activity of interferon-gamma- and interleukin-13-treated murine peritoneal macrophages.
We studied the effects of interferon-gamma (IFN-gamma), a Th1 cytokine, and interleukin-13 (IL-13) or interleukin-4 (IL-4), Th2 cytokines, on the antifungal activity of resident murine peritoneal macrophages against Candida albicans 'in vitro'. IFN-gamma, IL-13 and IL-4 treatment enhanced the candidastatic functions of the macrophages. Reactive oxygen intermediates (ROIs) seem to be directly involved in the increase of anti-Candida activity in macrophages treated with Th1 or Th2 cytokines. Study of unopsonized C. albicans phagocytosis showed that IFN-gamma reduces the uptake process whereas the Th2 cytokines increase it. This difference is correlated to mannose receptor expression, which is decreased by IFN-gamma but increased by the Th2 cytokines. So, the effects on phagocytosis and candidastatic activity of IFN-gamma-treated macrophages are dissociated. In contrast, the phagocytic ability of macrophages pretreated 'in vitro' with IL-4 or IL-13 played a complementary role to the ROIs, in reduction of yeast proliferation by macrophages. In consequence, the macrophages treated with IL-13 and IL-4 develop a higher fungistatic activity than macrophages activated by IFN-gamma. Amphotericin B associated with IL-13 or IFN-gamma, but not with IL-4, enhanced the yeast growth inhibition activity of macrophages. The ROIs were involved in the additive effect of IFN-gamma with amphotericin B, whereas another mechanism was implicated in the increase of candidastatic activity of macrophages treated with IL-13 in association with amphotericin B.
Coste
Agnès
A
Laboratoire des Macrophages, Médiateurs de l'Inflammation et Interactions Cellulaires, UPRES-EA 2405, INSERM IFR 31, C.H.U., Rangueil, 1 avenue Jean Poulhès, Tolouse, France.
Linas
Marie D
MD
Cassaing
Sophie
S
Bernad
José
J
Chalmeton
Sandrine
S
Séguéla
Jean P
JP
Pipy
Bernard
B
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007371:Interferon-gamma / Q000494:pharmacology*; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D037181:Lectins, C-Type; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D014498:Uracil / Q000378:metabolism
D000935:Antifungal Agents; D000975:Antioxidants; D016207:Cytokines; D007202:Indicators and Reagents; D018793:Interleukin-13; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D015847:Interleukin-4; D009569:Nitric Oxide; D014498:Uracil; D000666:Amphotericin B; D007371:Interferon-gamma