Support of Paracoccidioides brasiliensis multiplication by human monocytes or macrophages: inhibition by activated phagocytes

Abstract

Summary. The interaction of human monocytes or monocyte-derived macrophages and yeast-form Paracoccidioides brasiliensis was studied in vitro. Yeast cells were readily ingested by adherent monocytes or macrophages. Multiplication of P. brasiliensis, measured by growth as colony forming units (cfu) on a supplemented medium with good plating efficiency, was greater in monocyte co-cultures compared to the number of cfu obtained from complete tissue-culture medium (CTCM). Multiplication increased with time in macrophage cocultures, e.g., from two-six-fold in 24 h to nine-fold in 72 h. Microscopic observations indicated that ingested yeast cells multiplied inside macrophages. When monocytes were treated with supernate cytokines (CK) from concanavalin-A-stimulated mononuclear cells, then co-cultured with P. brasiliensis, multiplication was significantly inhibited compared with control monocyte co-cultures. Treatment of macrophages-derived from monocytes by culture in vitro for 3 days-for a further 3 days with CK resulted in maximal inhibition of multiplication over the subsequent 72 h. Similarly, when monocyte-derived macrophages (after culture for 7 days) were treated for 3 days with recombinant human y-interferon (IFN; 300 U/ml) or CK they restricted multiplication of P. brasiliensis by 65% and 95%, respectively, compared with control macrophages. Antibody to IFN abrogated the effect of IFN or CK treatment. These findings show that ingested P. brasiliensis can multiply in human monocytes or macrophages and that this multiplication can be restricted by activated monocytes or macrophages.

Nitric Oxide Participation in the Fungicidal Mechanism of Gamma Interferon-Activated Murine Macrophages againstParacoccidioides brasiliensisConidia

“…The results presented here confirm the protective role of IFN-␥ in PCM, as previously demonstrated by several groups (5,10,33). Thus, this cytokine appears to be a major mediator of resistance against P. brasiliensis infection in mice, as it promotes the antifungal activity of the Ms through NO production.…”

“…Treatment with lymphokine-containing supernatants from mitogen (concanavalin A)-stimulated spleen cells (8) or rIFN-␥ (5)-activated murine peritoneal Ms resulted in potent fungicidal activity against P. brasiliensis. Furthermore, treatment of human monocytes with cytokines, derived from supernatant of ConA-stimulated mononuclear cells and cocultured with the fungus, significantly inhibited multiplication compared to control monocytes (33). However, killing by activated murine Ms could not be abrogated by superoxide dismutase, catalase, or azide, suggesting that the fungicidal mechanism was independent of the oxidative burst products (5).…”

Paracoccidioidomycosis: an update

“…It has been shown that monocytes and monocyte-derived macrophages support the intracellular replication of ingested P. brasiliensis (199). However, monocyte-derived macrophages activated by gamma interferon (IFN-y; 300 U/ml, for 3 days) significantly (65 to 95%) inhibited the intracellular replication of ingested P. brasiliensis (199).…”

“…However, monocyte-derived macrophages activated by gamma interferon (IFN-y; 300 U/ml, for 3 days) significantly (65 to 95%) inhibited the intracellular replication of ingested P. brasiliensis (199). These (231).…”

Macrophage expression of class II major histocompatibility complex gene products in Paracoccidioides brasiliensis-infected mice.

“…1 The dimorphic fungus Paracoccidioides brasiliensis, the etiologic agent, is an intracellular parasite and parasitism of host mononuclear phagocytes is the central event in the dissemination of the disease. 2 Natural infections start by inhalation of conidia and/or mycelial fragments of the saprophytic phase. 3,4 The initial pulmonary lesions are asymptomatic in most cases, and may then regress spontaneously, become latent, or disseminate contiguously and/or via the lymphatics.…”