HOST DEFENSE AGAINST HISTOPLASMA CAPSULATUM IN AIDS

获得性免疫缺陷综合征是一种免疫调节剂 以卡波西氏肉瘤或 机会性感染。CD4+T细胞和单核巨噬细胞 是人类免疫缺陷病毒(HIV)的目标细胞， 艾滋病的病原体。单核/巨噬细胞(M-Phi)是 主要的艾滋病毒携带者，因此，一个严重的关切 宿主是M#从HIV+个体到M#的功能能力 消灭机会性病原体。播散性组织胞浆菌病 越来越频繁地被视为艾滋病的并发症， 特别是在组织胞浆菌(HC)流行的地区。 患有播散性组织胞浆菌病的艾滋病患者有较高的 即使在两性霉素治疗明显成功后也会复发 因此，我们当务之急是更好地了解 HIV+患者的HC与M-Phi的相互作用。 拟议的研究的目标是表征内在的 HIV感染者单核细胞/M-Phi功能缺陷 感染与他们防御HC的能力有关。这个 这项建议的具体目的是：L)量化 HIV感染者M-Phi结合和吞噬HC 酵母和微孢子与艾滋病毒感染者M-phi的比较；2) 以确定HIV感染患者的M-Phi是否提供了更多 比正常允许的环境下HC的转化率 微孢子进入致病酵母期，或允许更快 酵母菌比正常M-phi的增殖；3)量化 HIV感染者M-Phi被激活的能力 集落刺激因子(CSF)抑制细胞内 HC酵母菌的增殖与HIV-M-phi的比较 个人。 因为M-Phi功能的变化可能与疾病的进展相关 不仅是艾滋病毒感染，单核细胞/M-Phi将从 不同的患者群体，与艾滋病毒高危人群不同 感染但未感染艾滋病的患者。在……里面 此外，还将对感染的正常M-Phi进行研究 HIV在体外确定单独感染HIV是否会导致M-Phi 与HC的相互作用有关的功能障碍。

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.