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

We characterized the expression of the beta -chemokines macrophage inflamma tory protein 1 alpha (MIP-1 alpha), MIP-1 beta, and RANTES by primary human microglia after exposure to Cryptococcus neoformans. In the absence of spe cific antibody, C, neoformans failed to elicit a chemokine response, while in the presence of specific antibody, microglia produced MIP-1 alpha and MI P-1 beta in amounts comparable to those induced by lipopolysaccharide, RANT ES was also induced but at much lower levels. In addition to MIP-1 alpha an d MIP-1 beta mRNA, we observed a robust induction of monocyte chemoattracta nt protein 1 and interleukin-8 mRNA following incubation of microglia with opsonized C. neoformans, In contrast, cryptococcal polysaccharide did not i nduce a chemokine response even when specific antibody was present and inhi bited the MIP-1 alpha induction associated with antibody-mediated phagocyto sis 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 affe ct MIP-1 alpha induction. In contrast, treatment with herbimycin A, a tyros ine kinase inhibitor, inhibited MIP-1 alpha induction. Microglia stimulated with immobilized murine immunoglobulin also produced MIP-1 alpha and RANTE S (MIP-1 alpha > RANTES), Our results show that microglia produce several c hemokines when stimulated by C. neoformans in the presence of specific anti body and that this process is likely to be mediated by Fc receptor activati on. This response can be down-regulated by cryptococcal capsular polysaccha ride. 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.