Chaturvedi S, Newman S L
Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
J Clin Invest. 1997 Sep 15;100(6):1465-74. doi: 10.1172/JCI119667.
We have demonstrated that monocyte-derived macrophages (Mphi) from HIV+ individuals are deficient in their capacity to phagocytose Histoplasma capsulatum (Hc) yeasts, and are more permissive for the intracellular growth of Hc. To determine whether these defects in Mphi function were caused by HIV infection of the Mphi and/or by pathological events associated with HIV infection, cultured normal human Mphi were infected with the HIV-1BaL strain. Virus production, quantified by reverse transcriptase activity and p24 antigen, was evident on day 8 after infection and peaked on day 16. On days 12, 16, and 20 after infection, HIV-1-infected Mphi were deficient in their capacity to recognize and bind Hc yeasts compared with control Mphi, and also were more permissive for the intracellular growth of Hc. Culture of normal Mphi with the envelope glycoprotein gp120 inhibited phagocytosis of Hc yeasts by Mphi in a concentration-dependent manner, but did not cause more rapid intracellular growth of Hc. Normal Mphi cultured in the serum of HIV+ individuals with impaired Mphi function subsequently were deficient in their capacity to phagocytose Hc yeasts, and were more permissive for the intracellular growth of yeasts compared with Mphi cultured in normal serum. Conversely, culture of normal Mphi in the serum of HIV+ patients with normal Mphi function did not affect the interaction of Hc yeasts with Mphi. Moreover, when Mphi from HIV+ individuals that were initially defective in host defense against Hc were cultured in normal HIV- serum, normal Mphi function was demonstrated. Adsorption of gp120 from the serum of two HIV+ patients removed the capacity of the serum to cause a Mphi defect in phagocytosis of Hc, but had no effect on the capacity of the serum to cause accelerated intracellular growth. These data demonstrate that observed defects in Mphi interaction with Hc yeasts may be caused by gp120 and other, as yet unknown serum component(s) probably released into serum by HIV-infected cells.
我们已经证明，来自HIV阳性个体的单核细胞衍生巨噬细胞（Mphi）吞噬荚膜组织胞浆菌（Hc）酵母的能力存在缺陷，并且对Hc的细胞内生长更具易感性。为了确定Mphi功能的这些缺陷是由Mphi的HIV感染和/或与HIV感染相关的病理事件引起的，将培养的正常人Mphi用HIV-1BaL株感染。通过逆转录酶活性和p24抗原定量的病毒产生在感染后第8天明显，并在第16天达到峰值。在感染后第12、16和20天，与对照Mphi相比，HIV-1感染的Mphi识别和结合Hc酵母的能力存在缺陷，并且对Hc的细胞内生长也更具易感性。用包膜糖蛋白gp120培养正常Mphi以浓度依赖性方式抑制Mphi对Hc酵母的吞噬作用，但不会导致Hc在细胞内更快生长。在Mphi功能受损的HIV阳性个体的血清中培养的正常Mphi随后吞噬Hc酵母的能力存在缺陷，并且与在正常血清中培养的Mphi相比，对酵母的细胞内生长更具易感性。相反，在Mphi功能正常的HIV阳性患者的血清中培养正常Mphi不会影响Hc酵母与Mphi的相互作用。此外，当初始时对Hc宿主防御存在缺陷的HIV阳性个体的Mphi在正常HIV血清中培养时，表现出正常的Mphi功能。从两名HIV阳性患者的血清中吸附gp120消除了血清导致Mphi吞噬Hc缺陷的能力，但对血清导致细胞内生长加速的能力没有影响。这些数据表明，观察到的Mphi与Hc酵母相互作用的缺陷可能是由gp120和其他可能由HIV感染细胞释放到血清中的未知血清成分引起的。
