During Aspergillus infection, monocyte-derived DCs, neutrophils, and plasmacytoid DCs enhance innate immune defense through CXCR3-dependent crosstalk Journal Article


Authors: Guo, Y.; Kasahara, S.; Jhingran, A.; Tosini, N. L.; Zhai, B.; Aufiero, M. A.; Mills, K. A. M.; Gjonbalaj, M.; Espinosa, V.; Rivera, A.; Luster, A. D.; Hohl, T. M.
Article Title: During Aspergillus infection, monocyte-derived DCs, neutrophils, and plasmacytoid DCs enhance innate immune defense through CXCR3-dependent crosstalk
Abstract: Aspergillus fumigatus, a ubiquitous mold, is a common cause of invasive aspergillosis (IA) in immunocompromised patients. Host defense against IA relies on lung-infiltrating neutrophils and monocyte-derived dendritic cells (Mo-DCs). Here, we demonstrate that plasmacytoid dendritic cells (pDCs), which are prototypically antiviral cells, participate in innate immune crosstalk underlying mucosal antifungal immunity. Aspergillus-infected murine Mo-DCs and neutrophils recruited pDCs to the lung by releasing the CXCR3 ligands, CXCL9 and CXCL10, in a Dectin-1 and Card9- and type I and III interferon signaling-dependent manner, respectively. During aspergillosis, circulating pDCs entered the lung in response to CXCR3-dependent signals. Via targeted pDC ablation, we found that pDCs were essential for host defense in the presence of normal neutrophil and Mo-DC numbers. Although interactions between pDC and fungal cells were not detected, pDCs regulated neutrophil NADPH oxidase activity and conidial killing. Thus, pDCs act as positive feedback amplifiers of neutrophil effector activity against inhaled mold conidia. © 2020 Elsevier Inc. Guo et al. describe innate immune crosstalk in the lung during respiratory fungal infection. Infected neutrophils and Mo-DCs release CXCL9 and -10, recruiting CXCR3+ pDCs to the lung. In turn, pDCs enhance neutrophil antifungal activity and act as a positive feedback amplifier to promote the clearance of inhaled mold conidia. © 2020 Elsevier Inc.
Keywords: neutrophil; lung; innate immunity; fungus; aspergillus fumigatus; cxcl10; cxcl9; cxcr3; monocyte-derived dendritic cell; plasmacytoid dc
Journal Title: Cell Host & Microbe
Volume: 28
Issue: 1
ISSN: 1931-3128
Publisher: Cell Press  
Date Published: 2020-07-08
Start Page: 104
End Page: 116.e4
Language: English
DOI: 10.1016/j.chom.2020.05.002
PUBMED: 32485165
PROVIDER: scopus
PMCID: PMC7263227
DOI/URL:
Notes: Article -- Export Date: 3 August 2020 -- Source: Scopus
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MSK Authors
  1. Tobias Martin Hohl
    76 Hohl
  2. Bing   Zhai
    8 Zhai
  3. Nicholas Lepard Tosini
    4 Tosini
  4. Yahui Guo
    1 Guo
  5. Kathleen Mills
    2 Mills