TY - JOUR
T1 - Immunomodulatory properties of antifungal agents on phagocytic cells
AU - Simitsopoulou, Maria
AU - Roilides, Emmanuel
AU - Walsh, Thomas J.
N1 - Funding Information:
Declaration of interest: Dr. Walsh has served as consultant or received research grants from the Astellas, iCo, Novartis, Sigma Tau, Trius, and Vesta-gen. Dr. Roilides has received research grants from Pfizer, Gilead, Enzon, Novartis and has served as speaker for Gilead, Cephalon, Pfizer, Novartis, Merck. Dr. Simitsopoulou has no potential conflict of interest. The authors are responsible for the writing of this article.
PY - 2011
Y1 - 2011
N2 - Phagocytic cells, particularly neutrophils and monocytes/macrophages, are the first line and the most effective form of innate host defence against pathogenic fungi. During antifungal therapy these phagocytic cells are also exposed to antifungal agents. In the phagocyte-fungus-antifungal agent interplay, drugs may directly interact with phagocytes through specific pattern recognition receptors, leading to altered antifungal activities. Antifungal agents, through modulation of fungal virulence, may initiate different immune response programs in the phagocytes, leading to antifungal synergism/antagonism or up-regulation of gene expression for a pro-inflammatory response. Additionally, indirect modulation of phagocyte behavior by pretreatment of neutrophils, monocytes, and macrophages with cytokines and exposure to antifungal agents have shown promising findings for combined drug-cytokine therapy that may improve treatment of life-threatening fungal diseases. In this review, we discuss the main in vitro and in vivo immunomodulatory effects of antifungal agents on phagocytes in response to pathogenic fungi, as well as we address underlying immunopharmacologic mechanisms and their potential impact on clinical outcome.
AB - Phagocytic cells, particularly neutrophils and monocytes/macrophages, are the first line and the most effective form of innate host defence against pathogenic fungi. During antifungal therapy these phagocytic cells are also exposed to antifungal agents. In the phagocyte-fungus-antifungal agent interplay, drugs may directly interact with phagocytes through specific pattern recognition receptors, leading to altered antifungal activities. Antifungal agents, through modulation of fungal virulence, may initiate different immune response programs in the phagocytes, leading to antifungal synergism/antagonism or up-regulation of gene expression for a pro-inflammatory response. Additionally, indirect modulation of phagocyte behavior by pretreatment of neutrophils, monocytes, and macrophages with cytokines and exposure to antifungal agents have shown promising findings for combined drug-cytokine therapy that may improve treatment of life-threatening fungal diseases. In this review, we discuss the main in vitro and in vivo immunomodulatory effects of antifungal agents on phagocytes in response to pathogenic fungi, as well as we address underlying immunopharmacologic mechanisms and their potential impact on clinical outcome.
KW - Antifungal agents
KW - Immunopharmacology
KW - Phagocytic cells
UR - http://www.scopus.com/inward/record.url?scp=80053948951&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80053948951&partnerID=8YFLogxK
U2 - 10.3109/08820139.2011.615877
DO - 10.3109/08820139.2011.615877
M3 - Review article
C2 - 21985307
AN - SCOPUS:80053948951
SN - 0882-0139
VL - 40
SP - 809
EP - 824
JO - Immunological Investigations
JF - Immunological Investigations
IS - 7-8
ER -