Dynamics of lung macrophage activation in response to helminth infection

Mark C. Siracusa, Joshua J. Reece, Joseph F. Urban, Alan Leroy Scott

Research output: Contribution to journalArticle

Abstract

Most of our understanding of the development and phenotype of alternatively activated macrophages (AAMs) has been obtained from studies investigating the response of bone marrow- and peritoneal-derived cells to IL-4 or IL-13 stimulation. Comparatively little is known about the development of AAMs in the lungs, and how the complex signals associated with pulmonary inflammation influence the AAM phenotype. Here, we use Nippostrongylus brasiliensis to initiate AAM development and define the dynamics of surface molecules, gene expression, and cell function of macrophages isolated from lung tissue at different times postinfection (PI). Initially, lung macrophages take on a foamy phenotype, up-regulate MHC and costimulatory molecules, express reduced levels of TNF and IL-12, and undergo proliferation. Cells isolated between days 8 and 15 PI adopt a dense, granular phenotype and exhibit reduced levels of costimulatory molecules and elevated levels of programmed death ligand-1 (PDL-1) and PDL-2 and an increase in IL-10 expression. Functionally, AAMs isolated on days 13-15 PI demonstrate an enhanced capacity to take up and sequester antigen. However, these same cells did not mediate antigen-specific T cell proliferation and dampened the proliferation of CD3/CD28-activated CD4+ T cells. These data indicate that the alternative activation of macrophages in the lungs, although initiated by IL-4/IL-13, is a dynamic process that is likely to be influenced by other immune and non-immune factors in the pulmonary environment.

Original languageEnglish (US)
Pages (from-to)1422-1433
Number of pages12
JournalJournal of Leukocyte Biology
Volume84
Issue number6
DOIs
StatePublished - Dec 1 2008

Fingerprint

Macrophage Activation
Helminths
Macrophages
Lung
Infection
Phenotype
Interleukin-13
Interleukin-4
Nippostrongylus
T-Lymphocytes
Antigens
Interleukin-12
Interleukin-10
Pneumonia
Up-Regulation
Bone Marrow
Cell Proliferation
Ligands
Gene Expression

Keywords

  • Alternatively activated
  • Arginase
  • FIZZ1
  • Hygiene hypothesis
  • Nematode
  • Pulmonary
  • YM1

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Dynamics of lung macrophage activation in response to helminth infection. / Siracusa, Mark C.; Reece, Joshua J.; Urban, Joseph F.; Scott, Alan Leroy.

In: Journal of Leukocyte Biology, Vol. 84, No. 6, 01.12.2008, p. 1422-1433.

Research output: Contribution to journalArticle

Siracusa, Mark C. ; Reece, Joshua J. ; Urban, Joseph F. ; Scott, Alan Leroy. / Dynamics of lung macrophage activation in response to helminth infection. In: Journal of Leukocyte Biology. 2008 ; Vol. 84, No. 6. pp. 1422-1433.
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