Cryptococcus neoformans induces macrophage inflammatory protein 1α (MIP-1α) and MIP-1β in human microglia: Role of specific antibody and soluble capsular polysaccharide

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

Research output: Contribution to journalArticle

29 Scopus citations

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 - Mar 14 2001

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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