Phenotype

Macrophage

Biology

Gene

Helminths

Arginase

Nippostrongylus brasiliensis

In vitro

Immunology

Arginine

CD11c

Heligmosomoides polygyrus

Monocyte

Cell biology

Amino acid

Genetics

Cell Reports

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.

Helminth resistance is mediated by differential activation of recruited monocyte-derived alveolar macrophages and arginine depletion