title: Host responses to melioidosis and tuberculosis are both dominated by interferon-mediated signaling.
abstract: Melioidosis (Burkholderia pseudomallei infection) is a common cause of community-acquired sepsis in Northeast Thailand and northern Australia. B. pseudomallei is a soil saprophyte endemic to Southeast Asia and northern Australia. The clinical presentation of melioidosis may mimic tuberculosis (both cause chronic suppurative lesions unresponsive to conventional antibiotics and both commonly affect the lungs). The two diseases have overlapping risk profiles (e.g., diabetes, corticosteroid use), and both B. pseudomallei and Mycobacterium tuberculosis are intracellular pathogens. There are however important differences: the majority of melioidosis cases are acute, not chronic, and present with severe sepsis and a mortality rate that approaches 50% despite appropriate antimicrobial therapy. By contrast, tuberculosis is characteristically a chronic illness with mortality <2% with appropriate antimicrobial chemotherapy. We examined the gene expression profiles of total peripheral leukocytes in two cohorts of patients, one with acute melioidosis (30 patients and 30 controls) and another with tuberculosis (20 patients and 24 controls). Interferon-mediated responses dominate the host response to both infections, and both type 1 and type 2 interferon responses are important. An 86-gene signature previously thought to be specific for tuberculosis is also found in melioidosis. We conclude that the host responses to melioidosis and to tuberculosis are similar: both are dominated by interferon-signalling pathways and this similarity means gene expression signatures from whole blood do not distinguish between these two diseases.
authors: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom. gavin.koh@gmail.com
authors: Gavin C K W
authors: GC
authors: Koh
authors: M Fernanda
authors: MF
authors: Schreiber
authors: Ruben
authors: R
authors: Bautista
authors: Rapeephan R
authors: RR
authors: Maude
authors: Susanna
authors: S
authors: Dunachie
authors: Direk
authors: D
authors: Limmathurotsakul
authors: Nicholas P J
authors: NP
authors: Day
authors: Gordon
authors: G
authors: Dougan
authors: Sharon J
authors: SJ
authors: Peacock
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008554:Melioidosis / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D055815:Young Adult
chemical_list: D007372:Interferons
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