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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-like macrophage (AM) phenotype, expressing both Siglec-F and CD11c, surround invading parasitic larvae and preferentially kill parasites in vitro. Monocyte-derived AMs (Mo-AMs) express type 2-associated markers and show distinct remodeling of the chromatin landscape relative to tissue-derived AMs. In particular, they express high amounts of Arg1 (arginase-1), 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.

Summary: Emphysema results in destruction of alveolar walls and enlargement of lung airspaces and has been shown to develop during helminth infections through IL-4R-independent mechanisms. We examined whether interleukin 17A (IL-17A) may instead modulate development of emphysematous pathology in mice infected with the helminth parasite Nippostrongylus brasiliensis. We found that transient elevations in IL-17A shortly after helminth infection triggered subsequent emphysema that destroyed alveolar structures. Furthermore, lung B cells, activated through IL-4R signaling, inhibited early onset of emphysematous pathology. IL-10 and other regulatory cytokines typically associated with B regulatory cell function did not play a major role in this response. Instead, at early stages of the response, B cells produced high levels of the tissue-protective protein, Resistin-like molecule α (RELMα), which then downregulated IL-17A expression. These studies show that transient elevations in IL-17A trigger emphysema and reveal a helminth-induced immune regulatory mechanism that controls IL-17A and the severity of emphysema. : Emphysema causes pathology that can compromise lung function, and mechanisms for reducing disease severity remain unclear. Using a helminth model, Chen et al. show that type 2 immune response triggers lung B cells to produce RELMα, which then downregulates IL-17 production in the lung to limit emphysema. Keywords: emphysema, IL-17, B lymphocytes, RELMα, helminth

We examined the activation and effector functions of lung macrophages in mediatingimmunity against helminth parasites. Using fate mapping mice, we showed thatmonocytes recruited to the lung assume an alveolar macrophage phenotype andcomprise as many as 10% of alveolar macrophages by 7 days after inoculation.Monocyte-derived alveolar macrophages assume distinct transcriptional and metabolicprofiles that include high levels of arginase expression and preferentially mediatehelminth damage, both of which are dependent on neutrophil help. In further studies,arginase was shown to mediate helminth killing through localized depletion of arginine.