title: Impaired CXCR1-dependent oxidative defence in active tuberculosis patients.
abstract: Much of the pronounced host inflammatory response that occurs in tuberculosis (TB) is related to failed immunity against the invading pathogen. The G-protein coupled receptors CXCR1 and CXCR2 are implicated in important signal transduction pathways in lung inflammatory responses. We investigated the expression and function of these receptors in a simple whole blood model from 24 patients with pulmonary TB and in subjects with latent TB infection (LTBI). Healthy controls were recruited from close contacts to the pulmonary index patients. We found that pulmonary TB patients had significantly increased CXCR1 expression on blood cells compared to LTBI subjects and controls (p < 0.001). In contrast, LTBI subjects had a significant increase in CXCR2 expression compared to pulmonary TB patients (p < 0.001) and controls (p < 0.01). Leukocyte function, measured as oxidative capacity, was decreased in pulmonary TB patients compared to LTBI and controls (p < 0.001) and correlated with the increased CXCR1 expression. Leukocyte recruitment, measured as the expression of microRNA-223 was increased in pulmonary TB patients compared to LTBI (p < 0.05). We found that variations in receptor expression are linked to disease progression and affect the immune response against Mycobacterium tuberculosis (Mtb).
authors: Translational Medicine, Department of Clinical Microbiology, Malmö, Sweden. Electronic address: nader.alaridah@med.lu.se.
authors: Nader
authors: N
authors: Alaridah
authors: Regional Department of Infectious Disease Control and Prevention, Malmö, Sweden; Infectious Disease Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden. Electronic address: niclas.winqvist@skane.se.
authors: Niclas
authors: N
authors: Winqvist
authors: Laboratory Medicine, Department of Microbiology, Immunology and Glycobiology, Lund, Sweden. Electronic address: gisela.hakansson@med.lu.se.
authors: Gisela
authors: G
authors: Håkansson
authors: Laboratory Medicine, Department of Microbiology, Immunology and Glycobiology, Lund, Sweden. Electronic address: erik.tenland@med.lu.se.
authors: Erik
authors: E
authors: Tenland
authors: Laboratory Medicine, Department of Microbiology, Immunology and Glycobiology, Lund, Sweden. Electronic address: anna.ronnholm@med.lu.se.
authors: Anna
authors: A
authors: Rönnholm
authors: Translational Medicine, Department of Clinical Microbiology, Malmö, Sweden; Clinical Microbiology, Regional and University Laboratories, Region Skåne, Sweden. Electronic address: erik.sturegard@med.lu.se.
authors: Erik
authors: E
authors: Sturegård
authors: Infectious Disease Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden. Electronic address: per.bjorkman@med.lu.se.
authors: Per
authors: P
authors: Björkman
authors: Translational Medicine, Department of Clinical Microbiology, Malmö, Sweden. Electronic address: Gabriela.godaly@med.lu.se.
authors: Gabriela
authors: G
authors: Godaly
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D035683:MicroRNAs / Q000097:blood; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D010586:Phagocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D010587:Phagocytosis; D011446:Prospective Studies; D023062:Receptors, Interleukin-8A / Q000097:blood / Q000276:immunology*; D023063:Receptors, Interleukin-8B / Q000097:blood / Q000276:immunology; D016897:Respiratory Burst; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology; D055815:Young Adult
chemical_list: D035683:MicroRNAs; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; C525067:MIR223, human
keywords: G-protein-coupled-receptors; Latent tuberculosis; Phagocytosis; Pulmonary tuberculosis