title: The alveolar microenvironment of patients infected with human immunodeficiency virus does not modify alveolar macrophage interactions with Streptococcus pneumoniae.
abstract: We 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-γ) 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. Toll-like 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-γ 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.
authors.affiliation: Pulmonary Immunology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom. sbgordon@liverpool.ac.uk
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
authors.forename: R Thomas
authors.initials: RT
authors.lastname: Jagoe
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Jarman
authors.forename: James C
authors.initials: JC
authors.lastname: North
authors.forename: Alison
authors.initials: A
authors.lastname: Pridmore
authors.forename: Janelisa
authors.initials: J
authors.lastname: Musaya
authors.forename: Neil
authors.initials: N
authors.lastname: French
authors.forename: Eduard E
authors.initials: EE
authors.lastname: Zijlstra
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Molyneux
authors.forename: Robert C
authors.initials: RC
authors.lastname: Read
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D046228:Microarray Analysis; D010587:Phagocytosis; D060888:Real-Time Polymerase Chain Reaction; D013296:Streptococcus pneumoniae / Q000276:immunology*; D055815:Young Adult