title: Bacterial lipopolysaccharide inhibits influenza virus infection of human macrophages and the consequent induction of CD8+ T cell immunity.
abstract: It is well established that infection with influenza A virus (IAV) facilitates secondary bacterial disease. However, there is a growing body of evidence that the microbial context in which IAV infection occurs can affect both innate and adaptive responses to the virus. To date, these studies have been restricted to murine models of disease and the relevance of these findings in primary human cells remains to be elucidated. Here, we show that pre-stimulation of primary human monocyte-derived macrophages (MDMs) with the bacterial ligand lipopolysaccharide (LPS) reduces the ability of IAV to infect these cells. The inhibition of IAV infection was associated with a reduced transcription of viral RNA and the ability of LPS to induce an anti-viral/type I interferon response in human MDMs. We demonstrated that this reduced rate of viral infection is associated with a reduced ability to present a model antigen to autologous CD8+ T cells. Taken together, these data provide the first evidence that exposure to bacterial ligands like LPS can play an important role in modulating the immune response of primary human immune cells towards IAV infection, which may then have important consequences for the development of the host's adaptive immune response.
authors: Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Vic., Australia.
authors: Kirsty R
authors: KR
authors: Short
authors: Marloes
authors: M
authors: Vissers
authors: Stan
authors: S
authors: de Kleijn
authors: Aldert L
authors: AL
authors: Zomer
authors: Katherine
authors: K
authors: Kedzierska
authors: Emma
authors: E
authors: Grant
authors: Patrick C
authors: PC
authors: Reading
authors: Peter W M
authors: PW
authors: Hermans
authors: Gerben
authors: G
authors: Ferwerda
authors: Dimitri A
authors: DA
authors: Diavatopoulos
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004285:Dogs; D005434:Flow Cytometry; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D007371:Interferon-gamma
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