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Infection and Immunity, March 2001, p. 1808-1815, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1808-1815.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Cryptococcus neoformans Induces Macrophage Inflammatory Protein 1alpha (MIP-1alpha ) and MIP-1beta in Human Microglia: Role of Specific Antibody and Soluble Capsular Polysaccharide

David Goldman,1,2,* Xianyuan Song,3 Ryuhei Kitai,3 Arturo Casadevall,2,4 Meng-Liang Zhao,3 and Sunhee C. Lee3

Departments of Pediatrics,1 Pathology,3 Medicine,4 and Microbiology and Immunology,2 Albert Einstein College of Medicine, Bronx, New York

Received 25 October 2000/Returned for modification 7 December 2000/Accepted 12 December 2000

We characterized the expression of the beta -chemokines macrophage inflammatory protein 1alpha (MIP-1alpha ), MIP-1beta , 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-1alpha and MIP-1beta in amounts comparable to those induced by lipopolysaccharide. RANTES was also induced but at much lower levels. In addition to MIP-1alpha and MIP-1beta 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-1alpha 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-1alpha induction. In contrast, treatment with herbimycin A, a tyrosine kinase inhibitor, inhibited MIP-1alpha induction. Microglia stimulated with immobilized murine immunoglobulin also produced MIP-1alpha and RANTES (MIP-1alpha  > RANTES). Our results show that microglia produce several chemokines when stimulated 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 capsular 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.

* Corresponding author. Mailing address: Department of Pediatrics, Golding 703, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-4259. Fax: (718) 430-8701. E-mail: dgoldma{at}aecom.yu.edu.

Infection and Immunity, March 2001, p. 1808-1815, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1808-1815.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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