AIDS ASSOCIATED PLEURAL INFECTION

艾滋病患者仍然主要死于呼吸道感染。细菌性脓胸伴化脓性微生物是艾滋病患者肺炎的常见并发症。虽然多种微生物可引起艾滋病患者的胸膜感染，但引起脓胸的最常见的微生物之一是金黄色葡萄球菌。这一假说认为，在细菌性脓胸中，募集的中性粒细胞是参与有效胸膜抗菌宿主防御的重要吞噬细胞。我们在CD4敲除小鼠中开发了一种模拟艾滋病患者细菌性脓胸的细菌脓胸模型。胸膜间皮细胞通过产生中性粒细胞激活和趋化趋化因子MIP-2在中性粒细胞募集中发挥关键作用，而在我们的葡萄球菌性脓肿小鼠模型中，KC通过抑制体内分化的趋化因子的产生，改变了胸膜中性粒细胞募集和细菌清除。巨噬细胞炎症蛋白-2 （MIP-2）和KC（小鼠gro- α）。CD4耗竭的抑制作用部分是由于Th1型干扰素γ (ifn - γ)和Th2型细胞因子白介素-10 （IL-10）之间的相对不平衡。我们将在体内和体外对我们的假设进行评估。通过CD4敲除小鼠体内葡萄球菌脓肿模型，我们将评估1TH和2TH细胞因子对MIP-2和KC的调节作用。在体外，我们将研究间皮细胞对金黄色葡萄球菌释放中性粒细胞趋化因子的反应及其调控。了解中性粒细胞向胸膜间隙募集的调节机制可能有助于我们了解艾滋病患者暴发性细菌性脓胸的病理生理学，并可能有助于开发增强宿主防御反应的治疗模式。

Patients with AIDS continue to die predominantly as a result of respiratory infections. Bacterial empyema with pyogenic organisms is a common complication of pneumonia in patients with AIDS. Though multiple organisms can cause pleural infections in patients with AIDS, one of the commonest organisms to cause empyema is Staphylococcus aureus. It is the hypothesis of this proposal that recruited neutrophils represent important phagocytic cells involved in effective pleural antibacterial host defense in bacterial empyema. We have developed a model of bacterial empyema in CD4 knockout mice that mimics bacterial empyema in patients with AIDS. Pleural mesothelial cells play a critical role in neutrophil recruitment by the production of neutrophil activating and chemotactic chemokines MIP-2, and KC in our murine model of staphylococcal empyema CD4 depletion alters pleural neutrophil recruitment and bacterial clearance by inhibition the in vivo compartmentalized production of the chemokines. Macrophage inflammatory protein-2 (MIP-2) and KC (murine gro-alpha). The inhibitory effect of CD4 depletion is in part due to the relative imbalance between Th1 type Interferon Gamma (IFN-gamma) and Th2 type cytokines, Interleukin-10 (IL-10). We will evaluate our hypothesis both in vivo and in vitro. Using an in vivo model of staphylococcal empyema in CD4, knockout mice, we will evaluate the regulation of MIP-2 and KC by 1TH and 2TH cytokines. In vitro, mesothelial cell responses to S. Aureus by release of neutrophil chemokines and their regulation will be studied. Understanding the mechanism of regulation of neutrophil recruitment to the pleural space may help us discern the pathophysiology of the fulminant bacterial empyema seen in patients with AIDS and may help develop therapeutic modalities that augment host defense responses.