Interleukin-4 suppresses antifungal activity of human mononuclear phagocytes against Candida albicans in association with decreased uptake of blastoconidia

Emmanuel Roilides, Isaac Kadiltsoglou, Anastasia Dimitriadou, Maria Hatzistilianou, Anna Manitsa, John Karpouzas, Philip A. Pizzo, Thomas J. Walsh

Research output: Contribution to journalArticle

Abstract

Pathogenesis of invasive candidiasis may involve regulatory activities of Th2 immunity on phagocytic host defenses. The effects of interleukin (IL)-4 on antifungal capacity of human mononuclear phagocytes against Candida albicans were studied. Incubation of adherent mononuclear leukocytes from healthy donors with IL-4 (1-5 ng ml-1) at 37°C for 2-4 days suppressed uptake of C. albicans blastoconidia in the presence of human serum (P ≤ 0.01), and anti-IL-4 inhibited its suppressive effect. The effect of IL-4 was protein synthesis-dependent. Interferon-γ (0.25-25 ng ml-1), granulocyte-macrophage colony-stimulating factor (CSF, 20 ng ml-1), macrophage-CSF (15 ng ml-1) but not IL-10 (100 ng ml-1) somewhat counteracted the suppressive effect of IL-4. In contrast, mannose receptor-mediated uptake of blastoconidia in the absence of serum was increased by IL-4. Killing of conidia was decreased after incubation of morphonuclear leukocytes with IL-4 for 2 days (P <0.05). While superoxide anion production in response to phorbol myristate acetate was decreased by IL-4 (P <0.05), it was not altered in response to blastoconidia and pseudohyphae. Morphonuclear leukocyte-induced pseudohyphal damage also remained unaltered. These findings suggest that IL-4 plays its detrimental role in invasive candidiasis by predominantly suppressing uptake and killing of blastoconidia by morphonuclear leukocytes. Anti-IL-4, IFN-γ, GM-CSF and M-CSF appear to counteract suppression of morphonuclear leukocyte phagocytic activity suggesting new approaches to the management of disseminated candidiasis.

Original languageEnglish (US)
Pages (from-to)169-180
Number of pages12
JournalFEMS Immunology and Medical Microbiology
Volume19
Issue number2
DOIs
StatePublished - Oct 1997
Externally publishedYes

Fingerprint

Phagocytes
Candida albicans
Human Activities
Interleukin-4
Macrophage Colony-Stimulating Factor
Leukocytes
Invasive Candidiasis
Granulocyte-Macrophage Colony-Stimulating Factor
Mononuclear Leukocytes
Fungal Spores
Candidiasis
Tetradecanoylphorbol Acetate
Serum
Interleukin-1
Superoxides
Interleukin-10
Interferons
Interleukin-2
Immunity
Macrophages

Keywords

  • Candida
  • Cytokine
  • Interleukin-4
  • Monocyte/macrophage
  • Uptake

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Infectious Diseases

Cite this

Interleukin-4 suppresses antifungal activity of human mononuclear phagocytes against Candida albicans in association with decreased uptake of blastoconidia. / Roilides, Emmanuel; Kadiltsoglou, Isaac; Dimitriadou, Anastasia; Hatzistilianou, Maria; Manitsa, Anna; Karpouzas, John; Pizzo, Philip A.; Walsh, Thomas J.

In: FEMS Immunology and Medical Microbiology, Vol. 19, No. 2, 10.1997, p. 169-180.

Research output: Contribution to journalArticle

Roilides, Emmanuel ; Kadiltsoglou, Isaac ; Dimitriadou, Anastasia ; Hatzistilianou, Maria ; Manitsa, Anna ; Karpouzas, John ; Pizzo, Philip A. ; Walsh, Thomas J. / Interleukin-4 suppresses antifungal activity of human mononuclear phagocytes against Candida albicans in association with decreased uptake of blastoconidia. In: FEMS Immunology and Medical Microbiology. 1997 ; Vol. 19, No. 2. pp. 169-180.
@article{b6bf071a5a1b45be96b063a7e73a20ab,
title = "Interleukin-4 suppresses antifungal activity of human mononuclear phagocytes against Candida albicans in association with decreased uptake of blastoconidia",
abstract = "Pathogenesis of invasive candidiasis may involve regulatory activities of Th2 immunity on phagocytic host defenses. The effects of interleukin (IL)-4 on antifungal capacity of human mononuclear phagocytes against Candida albicans were studied. Incubation of adherent mononuclear leukocytes from healthy donors with IL-4 (1-5 ng ml-1) at 37°C for 2-4 days suppressed uptake of C. albicans blastoconidia in the presence of human serum (P ≤ 0.01), and anti-IL-4 inhibited its suppressive effect. The effect of IL-4 was protein synthesis-dependent. Interferon-γ (0.25-25 ng ml-1), granulocyte-macrophage colony-stimulating factor (CSF, 20 ng ml-1), macrophage-CSF (15 ng ml-1) but not IL-10 (100 ng ml-1) somewhat counteracted the suppressive effect of IL-4. In contrast, mannose receptor-mediated uptake of blastoconidia in the absence of serum was increased by IL-4. Killing of conidia was decreased after incubation of morphonuclear leukocytes with IL-4 for 2 days (P <0.05). While superoxide anion production in response to phorbol myristate acetate was decreased by IL-4 (P <0.05), it was not altered in response to blastoconidia and pseudohyphae. Morphonuclear leukocyte-induced pseudohyphal damage also remained unaltered. These findings suggest that IL-4 plays its detrimental role in invasive candidiasis by predominantly suppressing uptake and killing of blastoconidia by morphonuclear leukocytes. Anti-IL-4, IFN-γ, GM-CSF and M-CSF appear to counteract suppression of morphonuclear leukocyte phagocytic activity suggesting new approaches to the management of disseminated candidiasis.",
keywords = "Candida, Cytokine, Interleukin-4, Monocyte/macrophage, Uptake",
author = "Emmanuel Roilides and Isaac Kadiltsoglou and Anastasia Dimitriadou and Maria Hatzistilianou and Anna Manitsa and John Karpouzas and Pizzo, {Philip A.} and Walsh, {Thomas J.}",
year = "1997",
month = "10",
doi = "10.1016/S0928-8244(97)00083-7",
language = "English (US)",
volume = "19",
pages = "169--180",
journal = "Pathogens and Disease",
issn = "2049-632X",
publisher = "John Wiley & Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Interleukin-4 suppresses antifungal activity of human mononuclear phagocytes against Candida albicans in association with decreased uptake of blastoconidia

AU - Roilides, Emmanuel

AU - Kadiltsoglou, Isaac

AU - Dimitriadou, Anastasia

AU - Hatzistilianou, Maria

AU - Manitsa, Anna

AU - Karpouzas, John

AU - Pizzo, Philip A.

AU - Walsh, Thomas J.

PY - 1997/10

Y1 - 1997/10

N2 - Pathogenesis of invasive candidiasis may involve regulatory activities of Th2 immunity on phagocytic host defenses. The effects of interleukin (IL)-4 on antifungal capacity of human mononuclear phagocytes against Candida albicans were studied. Incubation of adherent mononuclear leukocytes from healthy donors with IL-4 (1-5 ng ml-1) at 37°C for 2-4 days suppressed uptake of C. albicans blastoconidia in the presence of human serum (P ≤ 0.01), and anti-IL-4 inhibited its suppressive effect. The effect of IL-4 was protein synthesis-dependent. Interferon-γ (0.25-25 ng ml-1), granulocyte-macrophage colony-stimulating factor (CSF, 20 ng ml-1), macrophage-CSF (15 ng ml-1) but not IL-10 (100 ng ml-1) somewhat counteracted the suppressive effect of IL-4. In contrast, mannose receptor-mediated uptake of blastoconidia in the absence of serum was increased by IL-4. Killing of conidia was decreased after incubation of morphonuclear leukocytes with IL-4 for 2 days (P <0.05). While superoxide anion production in response to phorbol myristate acetate was decreased by IL-4 (P <0.05), it was not altered in response to blastoconidia and pseudohyphae. Morphonuclear leukocyte-induced pseudohyphal damage also remained unaltered. These findings suggest that IL-4 plays its detrimental role in invasive candidiasis by predominantly suppressing uptake and killing of blastoconidia by morphonuclear leukocytes. Anti-IL-4, IFN-γ, GM-CSF and M-CSF appear to counteract suppression of morphonuclear leukocyte phagocytic activity suggesting new approaches to the management of disseminated candidiasis.

AB - Pathogenesis of invasive candidiasis may involve regulatory activities of Th2 immunity on phagocytic host defenses. The effects of interleukin (IL)-4 on antifungal capacity of human mononuclear phagocytes against Candida albicans were studied. Incubation of adherent mononuclear leukocytes from healthy donors with IL-4 (1-5 ng ml-1) at 37°C for 2-4 days suppressed uptake of C. albicans blastoconidia in the presence of human serum (P ≤ 0.01), and anti-IL-4 inhibited its suppressive effect. The effect of IL-4 was protein synthesis-dependent. Interferon-γ (0.25-25 ng ml-1), granulocyte-macrophage colony-stimulating factor (CSF, 20 ng ml-1), macrophage-CSF (15 ng ml-1) but not IL-10 (100 ng ml-1) somewhat counteracted the suppressive effect of IL-4. In contrast, mannose receptor-mediated uptake of blastoconidia in the absence of serum was increased by IL-4. Killing of conidia was decreased after incubation of morphonuclear leukocytes with IL-4 for 2 days (P <0.05). While superoxide anion production in response to phorbol myristate acetate was decreased by IL-4 (P <0.05), it was not altered in response to blastoconidia and pseudohyphae. Morphonuclear leukocyte-induced pseudohyphal damage also remained unaltered. These findings suggest that IL-4 plays its detrimental role in invasive candidiasis by predominantly suppressing uptake and killing of blastoconidia by morphonuclear leukocytes. Anti-IL-4, IFN-γ, GM-CSF and M-CSF appear to counteract suppression of morphonuclear leukocyte phagocytic activity suggesting new approaches to the management of disseminated candidiasis.

KW - Candida

KW - Cytokine

KW - Interleukin-4

KW - Monocyte/macrophage

KW - Uptake

UR - http://www.scopus.com/inward/record.url?scp=0030684042&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030684042&partnerID=8YFLogxK

U2 - 10.1016/S0928-8244(97)00083-7

DO - 10.1016/S0928-8244(97)00083-7

M3 - Article

C2 - 9395062

AN - SCOPUS:0030684042

VL - 19

SP - 169

EP - 180

JO - Pathogens and Disease

JF - Pathogens and Disease

SN - 2049-632X

IS - 2

ER -