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Monocyte-derived alveolar macrophages mediate resistance to migrating helminths through depletion of arginine availability

Fei Chen, Darine W. El Naccache, John Ponessa, Alexander Lemenze, Vanessa Espinosa, Wenhui Wu, Katherine Lothstein, Linhua Jin, Amariliz Rivera, Mark Siracusa, View ORCID ProfileWilliam C. Gause
doi: https://doi.org/10.1101/2020.10.02.322388
Fei Chen
1Center for Immunity and Inflammation, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
2Department of Medicine, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
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Darine W. El Naccache
1Center for Immunity and Inflammation, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
2Department of Medicine, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
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John Ponessa
1Center for Immunity and Inflammation, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
2Department of Medicine, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
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Alexander Lemenze
1Center for Immunity and Inflammation, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
4Department of Pathology, Immunology, and Laboratory Medicine, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
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Vanessa Espinosa
1Center for Immunity and Inflammation, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
5Department of Pediatrics, New Jersey Medical School, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
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Wenhui Wu
1Center for Immunity and Inflammation, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
2Department of Medicine, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
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Katherine Lothstein
1Center for Immunity and Inflammation, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
2Department of Medicine, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
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Linhua Jin
1Center for Immunity and Inflammation, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
2Department of Medicine, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
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Amariliz Rivera
1Center for Immunity and Inflammation, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
5Department of Pediatrics, New Jersey Medical School, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
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Mark Siracusa
1Center for Immunity and Inflammation, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
2Department of Medicine, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
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William C. Gause
1Center for Immunity and Inflammation, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
2Department of Medicine, Rutgers—The State University of New Jersey, Newark, New Jersey, USA
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  • ORCID record for William C. Gause
  • For correspondence: gausewc@njms.rutgers.edu
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Abstract

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

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 02, 2020.
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Monocyte-derived alveolar macrophages mediate resistance to migrating helminths through depletion of arginine availability
Fei Chen, Darine W. El Naccache, John Ponessa, Alexander Lemenze, Vanessa Espinosa, Wenhui Wu, Katherine Lothstein, Linhua Jin, Amariliz Rivera, Mark Siracusa, William C. Gause
bioRxiv 2020.10.02.322388; doi: https://doi.org/10.1101/2020.10.02.322388
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Monocyte-derived alveolar macrophages mediate resistance to migrating helminths through depletion of arginine availability
Fei Chen, Darine W. El Naccache, John Ponessa, Alexander Lemenze, Vanessa Espinosa, Wenhui Wu, Katherine Lothstein, Linhua Jin, Amariliz Rivera, Mark Siracusa, William C. Gause
bioRxiv 2020.10.02.322388; doi: https://doi.org/10.1101/2020.10.02.322388

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