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Ablation of the leptin receptor in myeloid cells impairs pulmonary clearance of Streptococcus pneumoniae and alveolar macrophage bactericidal function.

Publication ,  Journal Article
Mancuso, P; Curtis, JL; Freeman, CM; Peters-Golden, M; Weinberg, JB; Myers, MG
Published in: Am J Physiol Lung Cell Mol Physiol
July 1, 2018

Leptin is a pleiotropic hormone produced by white adipose tissue that regulates appetite and many physiological functions, including the immune response to infection. Genetic leptin deficiency in humans and mice impairs host defenses against respiratory tract infections. Since leptin deficiency is associated with obesity and other metabolic abnormalities, we generated mice that lack the leptin receptor (LepRb) in cells of the myeloid linage (LysM-LepRb-KO) to evaluate its impact in lean metabolically normal mice in a murine model of pneumococcal pneumonia. We observed higher lung and spleen bacterial burdens in LysM-LepRb-KO mice following an intratracheal challenge with Streptococcus pneumoniae. Although numbers of leukocytes recovered from bronchoalveolar lavage fluid did not differ between groups, we did observe higher levels of pulmonary IL-13 and TNFα in LysM-LepRb-KO mice 48 h post infection. Phagocytosis and killing of ingested S. pneumoniae were also impaired in alveolar macrophages (AMs) from LysM-LepRb-KO mice in vitro and were associated with reduced LTB4 and enhanced PGE2 synthesis in vitro. Pretreatment of AMs with LTB4 and the cyclooxygenase inhibitor, indomethacin, restored phagocytosis but not bacterial killing in vitro. These results confirm our previous observations in leptin-deficient ( ob/ob) and fasted mice and demonstrate that decreased leptin action, as opposed to metabolic irregularities associated with obesity or starvation, is responsible for the defective host defense against pneumococcal pneumonia. They also provide novel targets for therapeutic intervention in humans with bacterial pneumonia.

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Published In

Am J Physiol Lung Cell Mol Physiol

DOI

EISSN

1522-1504

Publication Date

July 1, 2018

Volume

315

Issue

1

Start / End Page

L78 / L86

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Streptococcus pneumoniae
  • Respiratory System
  • Receptors, Leptin
  • Pneumonia, Pneumococcal
  • Phagocytosis
  • Mice, Knockout
  • Mice
  • Macrophages
  • Lung
 

Citation

APA
Chicago
ICMJE
MLA
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Mancuso, P., Curtis, J. L., Freeman, C. M., Peters-Golden, M., Weinberg, J. B., & Myers, M. G. (2018). Ablation of the leptin receptor in myeloid cells impairs pulmonary clearance of Streptococcus pneumoniae and alveolar macrophage bactericidal function. Am J Physiol Lung Cell Mol Physiol, 315(1), L78–L86. https://doi.org/10.1152/ajplung.00447.2017
Mancuso, Peter, Jeffrey L. Curtis, Christine M. Freeman, Marc Peters-Golden, Jason B. Weinberg, and Martin G. Myers. “Ablation of the leptin receptor in myeloid cells impairs pulmonary clearance of Streptococcus pneumoniae and alveolar macrophage bactericidal function.Am J Physiol Lung Cell Mol Physiol 315, no. 1 (July 1, 2018): L78–86. https://doi.org/10.1152/ajplung.00447.2017.
Mancuso P, Curtis JL, Freeman CM, Peters-Golden M, Weinberg JB, Myers MG. Ablation of the leptin receptor in myeloid cells impairs pulmonary clearance of Streptococcus pneumoniae and alveolar macrophage bactericidal function. Am J Physiol Lung Cell Mol Physiol. 2018 Jul 1;315(1):L78–86.
Mancuso, Peter, et al. “Ablation of the leptin receptor in myeloid cells impairs pulmonary clearance of Streptococcus pneumoniae and alveolar macrophage bactericidal function.Am J Physiol Lung Cell Mol Physiol, vol. 315, no. 1, July 2018, pp. L78–86. Pubmed, doi:10.1152/ajplung.00447.2017.
Mancuso P, Curtis JL, Freeman CM, Peters-Golden M, Weinberg JB, Myers MG. Ablation of the leptin receptor in myeloid cells impairs pulmonary clearance of Streptococcus pneumoniae and alveolar macrophage bactericidal function. Am J Physiol Lung Cell Mol Physiol. 2018 Jul 1;315(1):L78–L86.

Published In

Am J Physiol Lung Cell Mol Physiol

DOI

EISSN

1522-1504

Publication Date

July 1, 2018

Volume

315

Issue

1

Start / End Page

L78 / L86

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Streptococcus pneumoniae
  • Respiratory System
  • Receptors, Leptin
  • Pneumonia, Pneumococcal
  • Phagocytosis
  • Mice, Knockout
  • Mice
  • Macrophages
  • Lung