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Alveolar macrophages from HIV-infected patients with pulmonary tuberculosis retain the capacity to respond to stimulation by lipopolysaccharide

Mwandumba, Henry ORCID:, Squire, Bertie ORCID:, White, S. A., Nyirenda, M. H., Zijlstra, E. E., Molyneux, Malcolm E, Russell, D. G. and Rhoades, E. R. (2007) 'Alveolar macrophages from HIV-infected patients with pulmonary tuberculosis retain the capacity to respond to stimulation by lipopolysaccharide'. Microbes and Infection, Vol 9, Issue 9, pp. 1053-1060.

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The functional capacity of alveolar macrophages (AM) in human immunodeficiency virus (HIV)-infected patients with pulmonary tuberculosis (TB) is not completely understood. To investigate the capacity of AM to mediate inflammatory responses, we obtained AM from human subjects by bronchoalveolar lavage (BAL) and studied the cells ex vivo. We compared AM from HIV-infected patients with suspected pulmonary TB to AM from healthy, HIV-negative controls for their capacity to produce TNF-alpha or 1L-6 spontaneously and upon stimulation with lipopolysaccharide (LPS). Cytokine-producing cells were identified by macrophage markers and intracellular cytokine staining and flow cytometry. A higher proportion of AM from patients with microbiologically confirmed pulmonary TB than patients with probable TB or controls spontaneously expressed TNF-a shortly after isolation (geometric means: 38.5%, 23.7% and 15.8%, respectively), suggesting endogenous cytokine production. The proportions of AM spontaneously expressing TNF-a positively correlated with peripheral blood CD4(+) T-lymphocyte counts in patients (partial r = 0.60, p =: 0.003) but not controls. Stimulation with LPS resulted in a significant increase in the proportions of TNF-alpha and 1L-6-positive AM from patients and controls (p < 0.01). Bronchoalveolar lavage fluid (BALF) from confirmed TB patients also contained higher concentrations of the inflammatory cytokines predominantly produced by macrophages, IL=6 and IL-8, than controls (geometric mean cytokine concentrations per gram of BALE albumin were 1291 pg/g vs. 115 pg/g, p = 0.03 for IL-6 and 4739 pg/g vs. 704 pg/g, p = 0.03 for IL-8). We concluded that.AM from HIV-infected patients with pulmonary TB produced and released inflammatory cytokines in vivo and retained their innate ability to respond to stimulation by LPS. (C) 2007 Elsevier Masson SAS. All rights reserved.

Item Type: Article
Uncontrolled Keywords: human alveolar macrophages pulmonary tuberculosis hiv cytokine production tnf-alpha il-6 acquired-immunodeficiency-syndrome necrosis-factor-alpha mycobacterium-tuberculosis in-vitro activation cells il-6 individuals monocytes cytokines
Subjects: QW Microbiology and Immunology > Immunity by Type > QW 568 Cellular immunity. Immunologic cytotoxicity. Immunocompetence. Immunologic factors (General)
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.5 Complications
WF Respiratory System > Tuberculosis > WF 300 Pulmonary tuberculosis
Faculty: Department: Groups (2002 - 2012) > Clinical Group
Digital Object Identifer (DOI):
Depositing User: Helen Rigby
Date Deposited: 05 May 2011 08:36
Last Modified: 17 Aug 2022 08:56


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