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

TM Hohl, A Rivera, L Lipuma, A Gallegos, C Shi… - Cell host & …, 2009 - cell.com
TM Hohl, A Rivera, L Lipuma, A Gallegos, C Shi, M Mack, EG Pamer
Cell host & microbe, 2009cell.com
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 …
Summary
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+Ly6Chi 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+Ly6Chi monocytes and their derivatives, revealing a compartmentally restricted function for these cells in adaptive respiratory immune responses.
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