Inflammatory monocytes facilitate adaptive CD4 T cell responses during respiratory fungal infection

Cell Host Microbe. 2009 Nov 19;6(5):470-81. doi: 10.1016/j.chom.2009.10.007.

Abstract

Aspergillus fumigatus, a ubiquitous fungus, causes invasive disease in immunocompromised humans. Although monocytes and antigen-specific CD4 T cells contribute to defense against inhaled fungal spores, how these cells interact during infection remains undefined. Investigating the role of inflammatory monocytes and monocyte-derived dendritic cells during fungal infection, we find that A. fumigatus infection induces an influx of chemokine receptor CCR2- and Ly6C-expressing inflammatory monocytes into lungs and draining lymph nodes. Depletion of CCR2(+) cells reduced A. fumigatus conidial transport from lungs to draining lymph nodes, abolished CD4 T cell priming following respiratory challenge, and impaired pulmonary fungal clearance. In contrast, depletion of CCR2(+)Ly6C(hi) monocytes during systemic fungal infection did not prevent CD4 T cell priming in the spleen. Our findings demonstrate that pulmonary CD4 T cell responses to inhaled spores require CCR2(+)Ly6C(hi) monocytes and their derivatives, revealing a compartmentally restricted function for these cells in adaptive respiratory immune responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens, Ly / immunology*
  • Antigens, Ly / metabolism
  • Aspergillus fumigatus*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Movement / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Inflammation
  • Lung / immunology
  • Lymph Nodes / immunology
  • Mice
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Pulmonary Aspergillosis / immunology*
  • Receptors, CCR2 / immunology*
  • Receptors, CCR2 / metabolism
  • Spleen / immunology

Substances

  • Antigens, Ly
  • Ly-6C antigen, mouse
  • Receptors, CCR2