International Immunology Advance Access originally published online on September 1, 2005
International Immunology 2005 17(11):1399-1408; doi:10.1093/intimm/dxh317
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Pulmonary Mycobacterium tuberculosis infection in leptin-deficient ob/ob mice
1 Laboratory of Experimental Internal Medicine, and 2 Department of Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
3 National Jewish Medical and Research Center, Denver, CO, USA
4 Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and Aids, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
5 Department of Human Nutrition, University of Illinois at Chicago, IL, USA
Correspondence to: C. W. Wieland; E-mail: c.wieland{at}amc.uva.nl
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 IFN
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 IFN 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
Keywords: lung, rodent, Th1 responses
Transmitting editor: Susan Swain
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