Exposure to bacterial products renders macrophages highly susceptible to T-tropic HIV-1.
Microbial coinfections variably influence HIV-1 infection through immune activation or direct interaction of microorganisms with HIV-1 or its target cells. In this study, we investigated whether exposure of macrophages to bacterial products impacts the susceptibility of these cells to HIV-1 of different cellular tropisms. We demonstrate that () macrophages exposed to bacterial cell wall components such as lipopolysaccharide (LPS) (Gram-negative rods), lipoteichoic acid (Gram-positive cocci), and lipoarabinomannan (Mycobacteria) become highly susceptible to T cell (T)-tropic HIV-1 (which otherwise poorly replicate in macrophages) and variably susceptible to macrophage (M)-tropic HIV-1; () LPS-stimulated macrophages secrete a number of soluble factors (i.e., chemokines, interferon, and proinflammatory cytokines) that variably affect HIV infection of macrophages, depending on the virus phenotype in question; and () LPS-stimulated macrophages express CCR5 (a major coreceptor for M-tropic HIV-1) at lower levels and CXCR4 (a major coreceptor for T-tropic HIV-1) at higher levels compared with unstimulated macrophages. We hypothesize that a more favorable environment for T-tropic HIV-1 and a less favorable or even unfavorable environment for M-tropic HIV-1 secondary to exposure of macrophages to those bacterial products may accerelate a transition from M- to T-tropic viral phenotype, which is indicative of disease progression.
Moriuchi
M
M
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. hmoriuchi@atlas.niaid.nih.gov
Moriuchi
H
H
Turner
W
W
Fauci
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AS
D002473:Cell Wall / Q000737:chemistry; D018925:Chemokines / Q000378:metabolism; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism; D006095:Gram-Positive Cocci / Q000276:immunology; D015497:HIV-1 / Q000145:classification / Q000472:pathogenicity*; D007372:Interferons / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D009161:Mycobacterium / Q000276:immunology; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019713:Receptors, CCR5 / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000821:virology; D013682:Teichoic Acids / Q000494:pharmacology; D014779:Virus Replication
D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D013682:Teichoic Acids; C050016:lipoarabinomannan; C009900:lipoteichoic acid; D007372:Interferons; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C