HOST DEFENSE AGAINST HISTOPLASMA CAPSULATUM IN AIDS

获得性免疫缺陷综合征（艾滋病）是一种免疫调节性疾病， 以卡波西肉瘤的存在为特征的疾病，或 机会性感染 CD 4 + T细胞和单核吞噬细胞 是人类免疫缺陷病毒（HIV）的靶细胞， 艾滋病的病原体。 单核细胞/巨噬细胞（M-phi）是 艾滋病毒的主要储存库，因此， 宿主是M#从HIV+个体到 消灭机会致病菌播散性组织胞浆菌病是 越来越多地被视为艾滋病的并发症， 特别是在荚膜组织胞浆菌（Hc）流行的地区。 艾滋病患者的播散性组织胞浆菌病有很高的 即使在用阿替霉素治疗明显成功后复发 B。 因此，我们必须更好地了解 Hc与来自HIV+患者的M-phi的相互作用。 拟议研究的目标是表征内在 HIV感染者单核细胞/M-phi功能缺陷 感染的能力，以抵御HC。 的 本建议的具体目标是：l）量化 HIV感染者的M-phi结合并吞噬Hc 酵母和小分生孢子与来自HIV个体的M-phi相比; 2） 为了确定来自HIV感染者的M-phi是否提供了更多的 比正常容许环境的Hc转化 小分生孢子进入致病酵母阶段，或允许更快 酵母菌比正常M-phi的增殖;和3）为了量化 HIV感染者的M-phi被激活的能力 集落刺激因子（CSF）抑制细胞内 与来自HIV的M-phi相比，Hc酵母菌的增殖- 个体 由于M-phi功能的变化可能与疾病进展相关 而不仅仅是HIV感染，单核细胞/M-phi将从 不同的患者群体，从那些谁是艾滋病毒的风险 感染但未感染艾滋病的人。 在 此外，还将对感染以下病毒的正常M-phi进行研究： HIV体外试验，以确定HIV单独感染是否会导致M-phi 与HC相互作用的功能障碍。

Acquired immunodeficiency syndrome (AIDS) is an immunoregulatory disorder characterized by the presence of Kaposi's sarcoma or opportunistic infections. CD4+ T cells and mononuclear phagocytes are the target cells for the human immuno- deficiency virus (HIV), the etiologic agent of AIDS. Monocyte/macrophages (M-phi) are the major reservoir of HIV and, therefore, a critical concern for the host is the functional capacity of M# from HIV+ individuals to destroy opportunistic pathogens. Disseminated histoplasmosis is seen with increasing frequency as a complication of AIDS, particularly in areas where Histoplasma capsulatum (Hc) is endemic. AIDS patients with disseminated histoplasmosis have a high rate of relapse even after apparently successful therapy with amphotericin B. Therefore, it is imperative that we gain a better understanding of the interaction of Hc with M-phi from HIV+ patients. The goal of the proposed study is to characterize the intrinsic defects in the function of monocyte/M-phi from patients with HIV infection with respect to their ability to defend against Hc. The specific aims of this proposal are: l) To quantify the capacity of M-phi from HIV-infected patients to bind and to phagocytose Hc yeasts and microconidia compared to M-phi from HIV- individuals; 2) To determine if M-phi from HIV-infected patients provide a more than normal permissive environment for the conversion of Hc microconidia into the pathogenic yeast phase, or permit more rapid multiplication of yeasts than normal M-phi; and 3) To quantify the capacity of M-phi from HIV-infected patients to be activated by colony stimulating factors (CSFs) to inhibit the intracellular multiplication of Hc yeasts compared to M-phi from HIV- individuals. As changes in M-phi function may correlate with disease progression and not merely HIV infection, monocyte/M-phi will be studied from different patient groups, from those who are at risk for HIV infection but who are not infected to patients with AIDS. In addition, studies will be performed on normal M-phi infected with HIV in vitro to determine if HIV infection alone can cause M-phi dysfunction with respect to its interaction with Hc.