CCR2 expression determines T1 versus T2 polarization during pulmonary Cryptococcus neoformans infection

J Immunol. 2000 Feb 15;164(4):2021-7. doi: 10.4049/jimmunol.164.4.2021.

Abstract

Pulmonary clearance of the encapsulated yeast Cryptococcus neoformans requires the development of T1-type immunity. The objective of this study was to determine the role of CCR2 in leukocyte recruitment and development of T1-type cell-mediated immunity during pulmonary C. neoformans infection. Intratracheal inoculation of C. neoformans into CCR2 knockout (CCR2-/-) mice produced a prolonged pulmonary infection (5000-fold CFU at 6 wk compared with CCR2+/+ mice) and significant dissemination to the spleen and brain (160- and 800-fold greater). In addition, CCR2 deficiency resulted in significantly reduced recruitment of macrophages (weeks 1-3) and CD8+ T cells (weeks 1-2) into the lungs. The immune response in CCR2-/- mice was characterized by chronic pulmonary eosinophilia, crystal deposition in the lungs, pulmonary leukocyte production of IL-4 and IL-5 but not IFN-gamma, lack of anticryptococcal delayed-type hypersensitivity, and high levels of serum IgE. These results demonstrate that expression of CCR2 is required for the development of a T1-type response to C. neoformans infection and lack of CCR2 results in a switch to a T2-type response. Thus, CCR2 plays a critical role in promoting the development of T1- over T2-type immune responses in the lung following cryptococcus infection.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Chemokine CCL2 / biosynthesis
  • Cryptococcosis / genetics
  • Cryptococcosis / immunology*
  • Cryptococcosis / microbiology
  • Cryptococcosis / pathology
  • Immunity, Cellular
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Lung Diseases, Fungal / genetics
  • Lung Diseases, Fungal / immunology*
  • Lung Diseases, Fungal / microbiology
  • Lung Diseases, Fungal / pathology
  • Lymphocyte Count
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, CCR2
  • Receptors, Chemokine / biosynthesis*
  • Receptors, Cytokine / biosynthesis*
  • Receptors, Cytokine / deficiency
  • Receptors, Cytokine / genetics
  • Time Factors

Substances

  • Ccr2 protein, mouse
  • Chemokine CCL2
  • Receptors, CCR2
  • Receptors, Chemokine
  • Receptors, Cytokine