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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. • Infected Mo-DCs and neutrophils secrete CXCL9 and -10 through Dectin-1 and IFN signaling • CXCL9 and -10 promote the entry of circulating CXCR3+ pDCs into the lung • Lung-infiltrating CXCR3+ pDCs are essential for host defense against A. fumigatus • pDCs activate neutrophil NADPH oxidase activity to promote sterilizing immunity 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. [ABSTRACT FROM AUTHOR]

Macrophages are known to mediate anti-helminth responses, but it remains uncertain which subsets are involved or how macrophages actually kill helminths. Here, we show rapid monocyte recruitment to the lung after infection with the nematode parasite Nippostrongylus brasiliensis. In this inflamed tissue microenvironment, these monocytes differentiate into an alveolar macrophage (AM)-like phenotype, expressing both SiglecF and CD11c, surround invading parasitic larvae, and preferentially kill parasites in vitro. Monocyte-derived AMs (Mo-AMs) express type 2-associated markers and show a distinct remodeling of the chromatin landscape relative to tissue-derived AMs (TD-AMs). In particular, they express high amounts of arginase-1 (Arg1), which we demonstrate mediates helminth killing through L-arginine depletion. These studies indicate that recruited monocytes are selectively programmed in the pulmonary environment to express AM markers and an anti-helminth phenotype., Competing Interests: Declaration of interests M.C.S. is the founder and President of NemaGen Discoveries., (Copyright © 2021 Rutgers University. Published by Elsevier Inc. All rights reserved.)