During Aspergillus infection, neutrophil, monocyte-derived DC, and plasmacytoid DC enhance innate immune defense through CXCR3-dependent crosstalk

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.

doi:10.1101/2020.05.05.079517

bioRxiv · 10.1101/2020.05.05.079517

During Aspergillus infection, neutrophil, monocyte-derived DC, and plasmacytoid DC enhance innate immune defense through CXCR3-dependent crosstalk

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.

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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 anti-viral 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/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.

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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.. 2020-05-05. During Aspergillus infection, neutrophil, monocyte-derived DC, and plasmacytoid DC enhance innate immune defense through CXCR3-dependent crosstalk. https://doi.org/10.1101/2020.05.05.079517

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