Pulmonary Mycobacterium tuberculosis infection in leptin-deficient ob/ob mice.
The development of active tuberculosis after infection with Mycobacterium tuberculosis is almost invariably caused by a persistent or transient state of relative immunodeficiency. Leptin, the product of the obese (ob) gene, is a pleiotropic protein produced mainly by adipocytes and is down-regulated during malnutrition and starvation, conditions closely connected with active tuberculosis. To investigate the role of leptin in tuberculosis, we intranasally infected wild-type (Wt) and leptin-deficient ob/ob mice with live virulent M. tuberculosis. Ob/ob mice displayed higher mycobacterial loads in the lungs after 5 and 10 weeks of infection, although the difference with Wt mice remained 1 log of M. tuberculosis colony forming unit. Nevertheless, ob/ob mice were less able to form well-shaped granuloma and lung lymphocyte numbers were reduced compared with Wt mice early during infection. In addition, ob/ob mice had a reduced capacity to produce the protective cytokine IFNgamma at the site of the infection early during infection and upon antigen-specific recall stimulation, and showed reduced delayed-type hypersensitivity reaction to intra-dermal tuberculin purified protein derivative. Leptin replacement restored the reduced IFNgamma response observed in ob/ob mice. Mortality did not differ between ob/ob and Wt mice. These data suggest that leptin plays a role in the early immune response to pulmonary tuberculosis.
Wieland
Catharina W
CW
Laboratory of Experimental Internal Medicine, and Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands. c.wieland@amc.uva.nl
Florquin
Sandrine
S
Chan
Edward D
ED
Leemans
Jaklien C
JC
Weijer
Sebastiaan
S
Verbon
Annelies
A
Fantuzzi
Giamila
G
van der Poll
Tom
T
D000818:Animals; D005786:Gene Expression Regulation / Q000276:immunology*; D015769:Granuloma, Respiratory Tract / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D020738:Leptin / Q000008:administration & dosage / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008820:Mice, Obese; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology
D020738:Leptin; D007371:Interferon-gamma