Inflammatory monocytes orchestrate innate antifungal immunity in the lung Journal Article

Authors: Espinosa, V.; Jhingran, A.; Dutta, O.; Kasahara, S.; Donnelly, R.; Du, P.; Rosenfeld, J.; Leiner, I.; Chen, C. C.; Ron, Y.; Hohl, T. M.; Rivera, A.
Article Title: Inflammatory monocytes orchestrate innate antifungal immunity in the lung
Abstract: Aspergillus fumigatus is an environmental fungus that causes invasive aspergillosis (IA) in immunocompromised patients. Although -CC-chemokine receptor-2 (CCR2) and Ly6C-expressing inflammatory monocytes (CCR2+Mo) and their derivatives initiate adaptive pulmonary immune responses, their role in coordinating innate immune responses in the lung remain poorly defined. Using conditional and antibody-mediated cell ablation strategies, we found that CCR2+Mo and monocyte-derived dendritic cells (Mo-DCs) are essential for innate defense against inhaled conidia. By harnessing fluorescent Aspergillus reporter (FLARE) conidia that report fungal cell association and viability in vivo, we identify two mechanisms by which CCR2+Mo and Mo-DCs exert innate antifungal activity. First, CCR2+Mo and Mo-DCs condition the lung inflammatory milieu to augment neutrophil conidiacidal activity. Second, conidial uptake by CCR2+Mo temporally coincided with their differentiation into Mo-DCs, a process that resulted in direct conidial killing. Our findings illustrate both indirect and direct functions for CCR2+Mo and their derivatives in innate antifungal immunity in the lung. © 2014 Espinosa et al.
Keywords: controlled study; nonhuman; flow cytometry; mouse; animal tissue; gene expression; dendritic cell; animal experiment; animal model; cell differentiation; histology; neutrophil; major histocompatibility antigen class 2; lung; reactive oxygen metabolite; natural killer cell; innate immunity; upregulation; monocyte; cxcl2 chemokine; conidium; chemokine receptor ccr2; interleukin 12; cxcl1 chemokine; cell selection; tumor necrosis factor; inducible nitric oxide synthase; antifungal activity; invasive aspergillosis; glycoprotein p 15095; reduced nicotinamide adenine dinucleotide phosphate oxidase; article
Journal Title: PLoS Pathogens
Volume: 10
Issue: 2
ISSN: 1553-7366
Publisher: Public Library of Science  
Date Published: 2014-02-20
Start Page: e1003940
Language: English
DOI: 10.1371/journal.ppat.1003940
PROVIDER: scopus
PMCID: PMC3930594
PUBMED: 24586155
Notes: Export Date: 1 August 2014 -- Source: Scopus
Citation Impact
MSK Authors
  1. Ingrid Leiner
    49 Leiner