Cryptococcus neoformans induces macrophage inflammatory protein 1α (MIP-1α) and MIP-1β in human microglia

Role of specific antibody and soluble capsular polysaccharide

David L. Goldman, X. Song, R. Kitai, A. Casadevall, M. L. Zhao, S. C. Lee

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

We characterized the expression of the β-chemokines macrophage inflammatory, protein 1α (MIP-1α), MIP-1β, and RANTES by primary human microglia after exposure to Cryptococcus neoformans. In the absence of specific antibody, C. neoformans failed to elicit a chemokine response, while in the presence of specific antibody, microglia produced MIP-1α and MIP-1β in amounts comparable to those induced by lipopolysaccharide. RANTES was also induced but at much lower levels. In addition to MIP-1α and MIP-1β mRNA, we observed a robust induction of monocyte chemoattractant protein 1 and interleukin-8 mRNA following incubation of microglia with opsonized C. neoformans. In contrast, cryptococcal polysaccharide did not induce a chemokine response even when specific antibody was present and inhibited the MIP-1α induction associated with antibody-mediated phagocytosis of C. neoformans. The role of the Fc receptor in the observed chemokine induction was explored in several experiments. Treatment of microglia with cytochalasin D inhibited internalization of C. neoformans but did not affect MIP-1α induction. In contrast, treatment with herbimycin A, a tyrosine kinase inhibitor, inhibited MIP-1α induction. Microglia stimulated with immobilized murine immunoglobulin also produced MIP-1α and RANTES (MIP-1α > RANTES). Our results show that microglia produce several chemokines when stimu1ated by C. neoformans in the presence of specific antibody and that this process is likely to be mediated by Fc receptor activation. This response can be down-regulated by cryptococcal capsu1ar polysaccharide. These findings suggest a mechanism by which C. neoformans infections fail to induce strong inflammatory responses in patients with cryptococcal meningoencephalitis and have important implications for antibody therapy.

Original languageEnglish (US)
Pages (from-to)1808-1815
Number of pages8
JournalInfection and Immunity
Volume69
Issue number3
DOIs
StatePublished - 2001

Fingerprint

Macrophage Inflammatory Proteins
Cryptococcus neoformans
Microglia
Polysaccharides
Antibodies
Chemokine CCL5
Chemokines
Fc Receptors
Cytochalasin D
Messenger RNA
Meningoencephalitis
Chemokine CCL2
Interleukin-8
Phagocytosis
Protein-Tyrosine Kinases
Lipopolysaccharides
Immunoglobulins
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Cryptococcus neoformans induces macrophage inflammatory protein 1α (MIP-1α) and MIP-1β in human microglia : Role of specific antibody and soluble capsular polysaccharide. / Goldman, David L.; Song, X.; Kitai, R.; Casadevall, A.; Zhao, M. L.; Lee, S. C.

In: Infection and Immunity, Vol. 69, No. 3, 2001, p. 1808-1815.

Research output: Contribution to journalArticle

@article{710cb8dff2d945b78ded20e28f009192,
title = "Cryptococcus neoformans induces macrophage inflammatory protein 1α (MIP-1α) and MIP-1β in human microglia: Role of specific antibody and soluble capsular polysaccharide",
abstract = "We characterized the expression of the β-chemokines macrophage inflammatory, protein 1α (MIP-1α), MIP-1β, and RANTES by primary human microglia after exposure to Cryptococcus neoformans. In the absence of specific antibody, C. neoformans failed to elicit a chemokine response, while in the presence of specific antibody, microglia produced MIP-1α and MIP-1β in amounts comparable to those induced by lipopolysaccharide. RANTES was also induced but at much lower levels. In addition to MIP-1α and MIP-1β mRNA, we observed a robust induction of monocyte chemoattractant protein 1 and interleukin-8 mRNA following incubation of microglia with opsonized C. neoformans. In contrast, cryptococcal polysaccharide did not induce a chemokine response even when specific antibody was present and inhibited the MIP-1α induction associated with antibody-mediated phagocytosis of C. neoformans. The role of the Fc receptor in the observed chemokine induction was explored in several experiments. Treatment of microglia with cytochalasin D inhibited internalization of C. neoformans but did not affect MIP-1α induction. In contrast, treatment with herbimycin A, a tyrosine kinase inhibitor, inhibited MIP-1α induction. Microglia stimulated with immobilized murine immunoglobulin also produced MIP-1α and RANTES (MIP-1α > RANTES). Our results show that microglia produce several chemokines when stimu1ated by C. neoformans in the presence of specific antibody and that this process is likely to be mediated by Fc receptor activation. This response can be down-regulated by cryptococcal capsu1ar polysaccharide. These findings suggest a mechanism by which C. neoformans infections fail to induce strong inflammatory responses in patients with cryptococcal meningoencephalitis and have important implications for antibody therapy.",
author = "Goldman, {David L.} and X. Song and R. Kitai and A. Casadevall and Zhao, {M. L.} and Lee, {S. C.}",
year = "2001",
doi = "10.1128/IAI.69.3.1808-1815.2001",
language = "English (US)",
volume = "69",
pages = "1808--1815",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - Cryptococcus neoformans induces macrophage inflammatory protein 1α (MIP-1α) and MIP-1β in human microglia

T2 - Role of specific antibody and soluble capsular polysaccharide

AU - Goldman, David L.

AU - Song, X.

AU - Kitai, R.

AU - Casadevall, A.

AU - Zhao, M. L.

AU - Lee, S. C.

PY - 2001

Y1 - 2001

N2 - We characterized the expression of the β-chemokines macrophage inflammatory, protein 1α (MIP-1α), MIP-1β, and RANTES by primary human microglia after exposure to Cryptococcus neoformans. In the absence of specific antibody, C. neoformans failed to elicit a chemokine response, while in the presence of specific antibody, microglia produced MIP-1α and MIP-1β in amounts comparable to those induced by lipopolysaccharide. RANTES was also induced but at much lower levels. In addition to MIP-1α and MIP-1β mRNA, we observed a robust induction of monocyte chemoattractant protein 1 and interleukin-8 mRNA following incubation of microglia with opsonized C. neoformans. In contrast, cryptococcal polysaccharide did not induce a chemokine response even when specific antibody was present and inhibited the MIP-1α induction associated with antibody-mediated phagocytosis of C. neoformans. The role of the Fc receptor in the observed chemokine induction was explored in several experiments. Treatment of microglia with cytochalasin D inhibited internalization of C. neoformans but did not affect MIP-1α induction. In contrast, treatment with herbimycin A, a tyrosine kinase inhibitor, inhibited MIP-1α induction. Microglia stimulated with immobilized murine immunoglobulin also produced MIP-1α and RANTES (MIP-1α > RANTES). Our results show that microglia produce several chemokines when stimu1ated by C. neoformans in the presence of specific antibody and that this process is likely to be mediated by Fc receptor activation. This response can be down-regulated by cryptococcal capsu1ar polysaccharide. These findings suggest a mechanism by which C. neoformans infections fail to induce strong inflammatory responses in patients with cryptococcal meningoencephalitis and have important implications for antibody therapy.

AB - We characterized the expression of the β-chemokines macrophage inflammatory, protein 1α (MIP-1α), MIP-1β, and RANTES by primary human microglia after exposure to Cryptococcus neoformans. In the absence of specific antibody, C. neoformans failed to elicit a chemokine response, while in the presence of specific antibody, microglia produced MIP-1α and MIP-1β in amounts comparable to those induced by lipopolysaccharide. RANTES was also induced but at much lower levels. In addition to MIP-1α and MIP-1β mRNA, we observed a robust induction of monocyte chemoattractant protein 1 and interleukin-8 mRNA following incubation of microglia with opsonized C. neoformans. In contrast, cryptococcal polysaccharide did not induce a chemokine response even when specific antibody was present and inhibited the MIP-1α induction associated with antibody-mediated phagocytosis of C. neoformans. The role of the Fc receptor in the observed chemokine induction was explored in several experiments. Treatment of microglia with cytochalasin D inhibited internalization of C. neoformans but did not affect MIP-1α induction. In contrast, treatment with herbimycin A, a tyrosine kinase inhibitor, inhibited MIP-1α induction. Microglia stimulated with immobilized murine immunoglobulin also produced MIP-1α and RANTES (MIP-1α > RANTES). Our results show that microglia produce several chemokines when stimu1ated by C. neoformans in the presence of specific antibody and that this process is likely to be mediated by Fc receptor activation. This response can be down-regulated by cryptococcal capsu1ar polysaccharide. These findings suggest a mechanism by which C. neoformans infections fail to induce strong inflammatory responses in patients with cryptococcal meningoencephalitis and have important implications for antibody therapy.

UR - http://www.scopus.com/inward/record.url?scp=0035112182&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035112182&partnerID=8YFLogxK

U2 - 10.1128/IAI.69.3.1808-1815.2001

DO - 10.1128/IAI.69.3.1808-1815.2001

M3 - Article

VL - 69

SP - 1808

EP - 1815

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 3

ER -