Expression of the leptin receptor outside of bone marrow-derived cells regulates tuberculosis control and lung macrophage MHC expression. Academic Article uri icon

Overview

abstract

  • Leptin is a pleiotropic hormone proposed to link nutritional status to the development of strong Th1 immunity. Because Mycobacterium tuberculosis control is affected by starvation and diabetes, we studied the role of the leptin receptor in regulating distinct immune cells during chronic infection. Infected db/db mice, bearing a natural mutation in the leptin receptor, have a markedly increased bacterial load in their lungs when compared with that of their wild-type counterparts. In response to M. tuberculosis infection, db/db mice exhibited disorganized granulomas, neutrophilia, and reduced B cell migration to the lungs, correlating with dysfunctional lung chemokine responses that include XCL1, CCL2, CXCL1, CXCL2, and CXCL13. In a db/db lung, myeloid cells were delayed in their production of inducible NO synthase and had reduced expression of MHC I and II. Although the Th1 cell response developed normally in the absence of leptin signaling, production of pulmonary IFN-γ was delayed and ineffective. Surprisingly, a proper immune response took place in bone marrow (BM) chimeras lacking leptin receptor exclusively in BM-derived cells, indicating that leptin acts indirectly on immune cells to modulate the antituberculosis response and bacterial control. Together, these findings suggest that the pulmonary response to M. tuberculosis is affected by the host's nutritional status via the regulation of non-BM-derived cells, not through direct action of leptin on Th1 immunity.

publication date

  • August 22, 2011

Research

keywords

  • Macrophages, Alveolar
  • Major Histocompatibility Complex
  • Receptors, Leptin
  • Tuberculosis

Identity

PubMed Central ID

  • PMC3178734

Scopus Document Identifier

  • 80053513143

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1003226

PubMed ID

  • 21859958

Additional Document Info

volume

  • 187

issue

  • 7