The Alveolar Microenvironment of Patients Infected with Human Immunodeficiency Virus Does Not Modify Alveolar Macrophage Interactions with Streptococcus pneumoniae

Abstract

gWe tested the hypothesis that HIV infection results in activation of alveolar macrophages and that this might be associated with impaired defense against pneumococcus. We compared alveolar macrophages and lymphocytes in 131 bronchoalveolar lavage samples from HIV-infected and healthy controls using inflammatory gene microarrays, flow cytometry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA) to determine the pattern of macrophage activation associated with HIV infection and the effect of this activation on defense against pneumococcus. We used gamma interferon (IFN-␥) priming to mimic the cellular milieu in HIV-infected lungs. InnateDB and BioLayout 3D were used to analyze the interactions of the upregulated genes. Alveolar macrophages from HIV-infected adults showed increased gene expression and cytokine production in a classical pattern. Bronchoalveolar lavage from HIV-infected subjects showed excess CD8 ؉ lymphocytes with activated phenotype. Tolllike receptor 4 (TLR4) expression was increased in macrophages from HIV-infected subjects, but function was similar between the groups; lung lavage fluid did not inhibit TLR function in transfected HeLa cells. Alveolar macrophages from HIV-infected subjects showed normal binding and internalization of opsonized pneumococci, with or without IFN-␥ priming. Alveolar macrophages from HIV-infected subjects showed classical activation compared to that of healthy controls, but this does not alter macrophage interactions with pneumococci.

Healthy HIV-1-Infected Individuals on Highly Active Antiretroviral Therapy Harbor HIV-1 in Their Alveolar Macrophages

“…[23][24][25] In humans, similar macrophage dysfunctions are seen 26,27 ; however, the data with respect to phagocytic functions are conflicting. [28][29][30][31] Gordon et al found that alveolar macrophages from healthy, nonsmoking HIV-1-infected adults showed normal internalization of opsonized pneumococci, 29 whereas others have shown that HIV-1-infected adults have impaired macrophage phagocytic capacity. 30,32,33 Most recently, Jambo et al found that HIV-1 present in small alveolar macrophages from asymptomatic HIV-1-infected HAART-naive individuals was associated with impaired phagocytic capacity and proteolytic activity.…”

Pulmonary Innate Immune Dysfunction in Human Immunodeficiency Virus

“…Given the noninfectious nature of that model, the findings suggest a prominent role for HIVrelated viral proteins in the pathogenesis of alveolar macrophage dysfunction. However, despite the clear abnormalities in macrophage function seen in HIV infection, the alveolar microenvironment of PLWHAs did not adversely affect macrophage responses to Streptococcus pneumoniae (27). Other investigators have found normal phagocytic function in the alveolar macrophages of PLWHAs, unless the patient abused tobacco as well (28).…”

Bacterial Respiratory Infections Complicating Human Immunodeficiency Virus

“…• Apparent selective infection and phagocytic dysfunction of a discrete subset of macrophages known as small alveolar macrophages, 24 as opposed to large alveolar macrophages which retain normal phagocytic function. 25 Phagosomal proteolytic activity, on the other hand, is defective in both types of alveolar macrophage irrespective of HIV infection of these cells. 24 • Neutropenia is commonly found in patients with advanced HIV infection 21 and may contribute to the heightened susceptibility for development of pneumonia caused by several bacterial pathogens, including Staphylococcus aureus in particular, as well as pneumococcus and various types of gram-negative pathogens.…”