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Intact Pneumococci Trigger Transcription of Interferon-Related Genes in Human Monocytes, while Fragmented, Autolyzed Bacteria Subvert This Response

Journal article
Authors Susann Skovbjerg
Rickard Nordén
Anna Martner
Ebba Samuelsson
Lars Hynsjö
Agnes E Wold
Published in Infection and Immunity
Volume 85
Issue 5
ISSN 0019-9567
Publication year 2017
Published at Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Institute of Biomedicine, Department of Infectious Medicine
Language en
Links doi.org/10.1128/iai.00960-16
Keywords Streptococcus pneumoniae, autolysins, inflammation, interferons, tumor-necrosis-factor, streptococcus-pneumoniae-infection, fucosyl-transferase genes, alveolar epithelial-cells, ifn-beta, production, endoplasmic-reticulum, i interferons, cytokine production, reduced virulence, nucleic-acids, Immunology, Infectious Diseases
Subject categories Immunology in the medical area, Infectious Medicine

Abstract

A peculiar trait of pneumococci (Streptococcus pneumoniae) is their propensity to undergo spontaneous lysis during stationary growth due to activation of the enzyme autolysin (LytA), which fragments the peptidoglycan cell wall. The fragments that are generated upon autolysis impair phagocytosis and reduce production of interleukin-12 (IL-12) and gamma interferon (IFN-gamma) by human leukocytes in response to intact pneumococci, thereby impeding crucial host defenses. The objective was to identify additional monocyte genes whose transcription is induced by intact pneumococci and subverted by autolyzed bacteria. Monocytes were isolated from healthy blood donors and stimulated for 3 h with UV-inactivated S. pneumoniae (Rx1PLY(-) LytA(+) strain), which is capable of autolyzing, its LytA(-) isogenic autolysin-deficient mutant, or a mixture of the two (containing twice the initial bacterial concentration). Gene expression was assessed by Illumina microarray, and selected findings were confirmed by reverse transcription-quantitative real-time PCR (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry. In all, we identified 121 genes that were upregulated to a significantly higher degree by intact than autolyzed pneumococci. These included IFNB1 and a large set of interferon-induced genes, such as IFIT3, RSAD2, CFCL1, and CXCL10 genes, as well as IL12B and CD40 genes. RT-qPCR revealed that transcription of these genes in response to intact pneumococci diminished when autolyzed pneumococci were admixed and that this pattern was independent of pneumolysin. Thus, transcription of interferon-related genes is triggered by intact pneumococci and subverted by fragments generated by spontaneous bacterial autolysis. We suggest that interferon-related pathways are important for elimination of pneumococci and that autolysis contributes to virulence by extinguishing these pathways.

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