title: Elevated serum CCL2 concomitant with a reduced mycobacterium-induced response leads to disease dissemination in leprosy.
abstract: Mycobacterium leprae and Mycobacterium tuberculosis are successful intracellular pathogens which down regulate host immune responses. T-cell interferon-gamma (IFNgamma) and macrophage tumour necrosis factor-alpha (TNFalpha) activate chemokines such as, C-C chemokine ligand-2 (CCL2) and CCL5, which play a role in granuloma formation. Lepromatous leprosy is characterized by defective granulomas with lowered T-cell- and macrophage-mediated responses. Tuberculosis (TB) can be localized to the lung, whereby discreet granulomas are formed. The role of chemokines in leprosy infections is as yet unclear. We compared chemokine responses in lepromatous leprosy and pulmonary tuberculosis patients. Circulating serum CCL2 was raised while CCL5 was lowered in leprosy, as compared with TB patients and healthy controls. However, both Mycobacterium bovis BCG- (P=0.08) and M. leprae-induced (P=0.05) CCL2 secretion was reduced in leprosy. In leprosy, BCG induced greater CCL2 (P=0.01), TNFalpha (P=0.02) and somewhat greater CCL5 (P=0.08) than M. leprae, while CXCL8 induction was comparable. Overall levels of Mycobacterium-induced CCL2, TNFalpha and CXCL8 were two to threefold lower, and CCL5 was 10-fold lower in leprosy as compared with TB. Reduced inducible CCL2 combined with a lowered TNFalpha response in lepromatous leprosy may contribute to the unrestricted growth and dissemination of mycobacteria found in the disease.
authors.affiliation: Department of Pathology and Microbiology, Aga Khan University, Karachi, Pakistan. zahra.hasan@aku.edu
authors.forename: Z
authors.initials: Z
authors.lastname: Hasan
authors.forename: B
authors.initials: B
authors.lastname: Jamil
authors.forename: I
authors.initials: I
authors.lastname: Zaidi
authors.forename: S
authors.initials: S
authors.lastname: Zafar
authors.forename: A A
authors.initials: AA
authors.lastname: Khan
authors.forename: R
authors.initials: R
authors.lastname: Hussain
mesh_terms: D000328:Adult; D000368:Aged; D001500:BCG Vaccine; D018932:Chemokine CCL2 / Q000097:blood*; D016207:Cytokines / Q000097:blood; D006801:Humans; D015440:Leprosy, Lepromatous / Q000276:immunology* / Q000382:microbiology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009163:Mycobacterium bovis; D009166:Mycobacterium leprae / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology
chemical_list: D001500:BCG Vaccine; D018932:Chemokine CCL2; D016207:Cytokines