HIV-1 Envelope Protein (gp120) Inhibits the Activity of Human Bronchoalveolar Macrophages againstCryptococcus neoformans

Abstract

Cryptococcus neoformans infections are a major cause of morbidity and mortality for HIV-infected persons. Containment of the initial respiratory inoculation to the lung appears defective in patients with AIDS despite the low burden of HIV in bronchoalveolar macrophages. We have studied the fungistatic activity of human bronchoalveolar macrophages (BAM) cultured with an encapsulated strain of C. neoformans in the presence of pooled human serum. We observed 51.6% fungistasis after 24 h of culture. Fungistasis was diminished if the pooled human serum was heat-inactivated but was not affected by anticryptococcal capsular IgG. HIV envelope protein (gp120) has been shown to interfere with lymphocyte activation in vitro. We studied the effects of gp120 on BAM function and found that fungistatic activity was inhibited 25% (p < 0.001). Although binding of yeasts was not affected, gp120 inhibited the internalization of bound yeasts by 46% (p = 0.025). These experiments indicate that gp120 decreases the internalization and fungistasis of C. neoformans by human BAM, and they suggest a mechanism to explain how a small number of HIV-1-infected cells in the lung could impair the containment of C. neoformans.

Modulation of the effector function of human macrophages for Histoplasma capsulatum by HIV-1. Role of the envelope glycoprotein gp120.

“…Likewise, Shiratsuchi et al (29) found that culture of human monocytes with gp120 for 2 d inhibited the phagocytosis of M. avium, and enhanced intracellular replication. Although the exact mechanism(s) is unknown, both reports demonstrated that the effects of gp120 were mediated, in part, through binding of gp120 to M CD4 (28,29). In agreement with the present study, the latter group also found that pretreatment with p24 did not affect monocyte interactions with M. avium.…”

“…Wagner et al (28) reported that culture of human alveolar M with rgp120 for 60 min decreased M fungistatic activity against C. neoformans, and decreased the ingestion of, but not the attachment of C. neoformans yeasts. Likewise, Shiratsuchi et al (29) found that culture of human monocytes with gp120 for 2 d inhibited the phagocytosis of M. avium, and enhanced intracellular replication.…”

“…Studies with other microorganisms have demonstrated that the envelope glycoprotein gp120 can modulate M phagocytosis and antimicrobial activity through binding to M CD4 receptors (28,29). Therefore, we sought to determine if gp120 might impair M interaction with Hc.…”

Envelope glycoprotein (gp120) from HIV-1 enhancesMycobacterium aviumgrowth in human bronchoalveolar macrophages; an effect mediated by enhanced prostaglandin synthesis

“…Wagner era/. [14] found that gpl 20 pulsing of macrophages inhibited the uptake of Cryptococcus neoformans. Recent data by Wahl et al [19] has shown that gpl20 triggers the copious release of PGF.2 from macrophages.…”

A CCR5-Dependent Novel Mechanism for Type 1 HIV gp120 Induced Loss of Macrophage Cell Surface CD4

“…There is also evidence that both T cell and APC function can be compromised in uninfected cells of HIV ϩ patients (13)(14)(15)(16)(17)(18)(19). HIV-1-associated alteration of APC function has downstream consequences for the generation of adaptive immune responses.…”