title: Human alveolar macrophage gene responses to Mycobacterium tuberculosis strains H37Ra and H37Rv.
abstract: H37Rv and H37Ra have been widely used as models of virulent and avirulent strains, respectively, of Mycobacterium tuberculosis. Since the sequencing of H37Rv, microarrays have been used to investigate gene expression of M. tuberculosis strains under various conditions, and to compare gene expression of specific isolates of the organism. Because differences in the virulence of these organisms could also be manifest via their differential induction of host genes, we used Affymetrix Human Genome Arrays U133A and U133B to evaluate human alveolar macrophage (AM) responses to infection with H37Rv and H37Ra. H37Rv altered expression of far more genes than did H37Ra. Moreover, the genes induced by H37Rv to a greater extent than by H37Ra were predominantly associated with the development of effective immunity. H37Rv markedly increased expression of IL-23 p19, whereas neither organism significantly induced IL-12 p35 expression. Quantitative PCR confirmed that H37Rv induced significantly more AM p19 expression than did H37Ra. After low-level infection of both AM and peripheral blood monocytes (MN) with H37Rv, neither cell type produced IL-12 (by ELISA). In contrast, AM displayed significant IL-23 production in response to H37Rv, whereas MN did not. Our findings thus suggest an important role for IL-23 in human host responses to pulmonary infection with M. tuberculosis, and are consistent with epidemiologic and genetic studies that imply that H37Rv may not have unusual capacity to cause human disease.
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Biomedical Research Building, Rm. 1030, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-4984, USA. rfs4@po.cwru.edu
authors.forename: Richard F
authors.initials: RF
authors.lastname: Silver
authors.forename: Jessica
authors.initials: J
authors.lastname: Walrath
authors.forename: Hung
authors.initials: H
authors.lastname: Lee
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Jacobson
authors.forename: Heidi
authors.initials: H
authors.lastname: Horton
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bowman
authors.forename: Karl
authors.initials: K
authors.lastname: Nocka
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Sypek
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000382:microbiology; D015536:Down-Regulation / Q000235:genetics; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D053759:Interleukin-23 / Q000096:biosynthesis; D042541:Intracellular Space / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000382:microbiology*; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D014376:Tuberculosis / Q000235:genetics / Q000382:microbiology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D053759:Interleukin-23; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
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