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 |
| DOI/URL: | |
| Notes: | Export Date: 1 August 2014 -- Source: Scopus |
