Beta-chemokines are induced by Mycobacterium tuberculosis and inhibit its growth.
Chemokines (CK) are potent leukocyte activators and chemoattractants and aid in granuloma formation, functions critical for the immune response to Mycobacterium tuberculosis. We hypothesized that infection of alveolar macrophages (AM) with different strains of M. tuberculosis elicits distinct profiles of CK, which could be altered by human immunodeficiency virus (HIV) infection. RANTES, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta were the major beta-CK produced in response to M. tuberculosis infection. Virulent M. tuberculosis (H37Rv) induced significantly less MIP-1 alpha than did the avirulent strain (H37Ra), while MIP-1 beta and RANTES production was comparable for both strains. MIP-1 alpha and MIP-1 beta were induced by the membrane, but not cytosolic, fraction of M. tuberculosis. M. tuberculosis-induced CK secretion was partly dependent on tumor necrosis factor alpha (TNF-alpha). AM from HIV-infected individuals produced less TNF-alpha and MIP-1 beta than did normal AM in response to either M. tuberculosis strain. We tested the functional significance of decreased beta-CK secretion by examining the ability of beta-CK to suppress intracellular growth of M. tuberculosis. MIP-1 beta and RANTES suppressed intracellular growth of M. tuberculosis two- to threefold, a novel finding. Thus, beta-CK contribute to the innate immune response to M. tuberculosis infection, and their diminution may promote the intracellular survival of M. tuberculosis.
Saukkonen
Jussi J
JJ
Pulmonary Care Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA. jsqukkonen@lung.bumc.bu.edu
Bazydlo
Beth
B
Thomas
Michael
M
Strieter
Robert M
RM
Keane
Joseph
J
Kornfeld
Hardy
H
D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis; D019742:Chemokines, CC / Q000096:biosynthesis*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D016676:Macrophages, Alveolar / Q000276:immunology / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha