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Fungi subvert vaccine T cell priming at the respiratory mucosa by preventing chemokine-induced influx of inflammatory monocytes.

Vaccinologists strive to harness immunity at mucosal sites of pathogen entry. We studied respiratory delivery of an attenuated vaccine against Blastomyces dermatitidis. We created a T cell receptor transgenic mouse responsive to vaccine yeast and found that mucosal vaccination led to poor T cell activation in the draining nodes and differentiation in the lung. Mucosal vaccination subverted lung T cell priming by inducing matrix metalloproteinase 2 (MMP2), which impaired the action of the chemokine CCL7 on egress of CCR2(+) Ly6C(hi) inflammatory monocytes from the bone marrow and their recruitment to the lung. Studies in Mmp2(-/-) mice, or treatment with MMP inhibitor or rCCL7, restored recruitment of Ly6C(hi) monocytes to the lung and CD4(+) T cell priming. Mucosal vaccination against fungi and perhaps other respiratory pathogens may require manipulation of host MMPs in order to alter chemokine signals needed to recruit Ly6C(hi) monocytes and prime T cells at the respiratory mucosa.

Pubmed ID: 22483803


  • W├╝thrich M
  • Ersland K
  • Sullivan T
  • Galles K
  • Klein BS



Publication Data

April 20, 2012

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01 AI040996
  • Agency: NIAID NIH HHS, Id: R01 AI040996-14
  • Agency: NIAID NIH HHS, Id: R01 AI093553
  • Agency: NIAID NIH HHS, Id: R01 AI093553-01A1
  • Agency: NIAID NIH HHS, Id: R37 AI035681

Mesh Terms

  • Animals
  • Antigens, Ly
  • Blastomyces
  • Bone Marrow Cells
  • CD4-Positive T-Lymphocytes
  • Cell Differentiation
  • Cell Line
  • Cell Movement
  • Chemokine CCL7
  • Fungal Vaccines
  • Inflammation
  • Lymphocyte Activation
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase Inhibitors
  • Mice
  • Mice, Transgenic
  • Monocytes
  • Respiratory Mucosa
  • Vaccination