Exposure of Monocytes to Lipoarabinomannan Promotes Their Differentiation into Functionally and Phenotypically Immature Macrophages.
Lipoarabinomannan (LAM) is a lipid virulence factor secreted by Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis. LAM can be measured in the urine or serum of tuberculosis patients (TB-patients). Circulating monocytes are the precursor cells of alveolar macrophages and might be exposed to LAM in patients with active TB. We speculated that exposing monocytes to LAM could produce phenotypically and functionally immature macrophages. To test our hypothesis, human monocytes were stimulated with LAM (24-120 hours) and various readouts were measured. The study showed that when monocytes were exposed to LAM, the frequency of CD68(+), CD33(+), and CD86(+) macrophages decreased, suggesting that monocyte differentiation into mature macrophages was affected. Regarding functionality markers, TLR2(+) and TLR4(+) macrophages also decreased, but the percentage of MMR(+) expression did not change. LAM-exposed monocytes generated macrophages that were less efficient in producing proinflammatory cytokines such as TNF-α and IFN-γ; however, their phagocytic capacity was not modified. Taken together, these data indicate that LAM exposure influenced monocyte differentiation and produced poorly functional macrophages with a different phenotype. These results may help us understand how mycobacteria can limit the quality of the innate and adaptive immune responses.
Laboratory of Integrative Immunology, National Institute of Respiratory Diseases Ismael Cosio Villegas, 14080 Mexico City, DF, Mexico.
Leslie
L
Chávez-Galán
Laboratory of Integrative Immunology, National Institute of Respiratory Diseases Ismael Cosio Villegas, 14080 Mexico City, DF, Mexico.
Ranferi
R
Ocaña-Guzmán
Department of Physiology, National Institute of Respiratory Diseases Ismael Cosio Villegas, 14080 Mexico City, DF, Mexico.
Luis
L
Torre-Bouscoulet
Department of Pulmonary Fibrosis, National Institute of Respiratory Diseases Ismael Cosio Villegas, 14080 Mexico City, DF, Mexico.
Carolina
C
García-de-Alba
Laboratory of Integrative Immunology, National Institute of Respiratory Diseases Ismael Cosio Villegas, 14080 Mexico City, DF, Mexico.
Isabel
I
Sada-Ovalle
D000954:Antigens, Surface / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010587:Phagocytosis; D010641:Phenotype; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
D000954:Antigens, Surface; D016207:Cytokines; D008070:Lipopolysaccharides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C050016:lipoarabinomannan