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Macrophage origin limits functional plasticity in helminth-bacterial co-infection

Research output: Contribution to journalJournal article

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  • Dominik Rückerl
  • Sharon M Campbell
  • Sheelagh Duncan
  • Tara E Sutherland
  • Stephen J Jenkins
  • James P Hewitson
  • Tom A Barr
  • Lucy H Jackson-Jones
  • Rick M Maizels
  • Judith E Allen
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Article numbere1006233
<mark>Journal publication date</mark>23/03/2017
<mark>Journal</mark>PLoS Pathogens
Issue number3
Volume13
Number of pages19
Publication StatusPublished
<mark>Original language</mark>English

Abstract

Rapid reprogramming of the macrophage activation phenotype is considered important in the defense against consecutive infection with diverse infectious agents. However, in the setting of persistent, chronic infection the functional importance of macrophage-intrinsic adaptation to changing environments vs. recruitment of new macrophages remains unclear. Here we show that resident peritoneal macrophages expanded by infection with the nematode Heligmosomoides polygyrus bakeri altered their activation phenotype in response to infection with Salmonella enterica ser. Typhimurium in vitro and in vivo. The nematode-expanded resident F4/80high macrophages efficiently upregulated bacterial induced effector molecules (e.g. MHC-II, NOS2) similarly to newly recruited monocyte-derived macrophages. Nonetheless, recruitment of blood monocyte-derived macrophages to Salmonella infection occurred with equal magnitude in co-infected animals and caused displacement of the nematode-expanded, tissue resident-derived macrophages from the peritoneal cavity. Global gene expression analysis revealed that although nematode-expanded resident F4/80high macrophages made an anti-bacterial response, this was muted as compared to newly recruited F4/80low macrophages. However, the F4/80high macrophages adopted unique functional characteristics that included enhanced neutrophil-stimulating chemokine production. Thus, our data provide important evidence that plastic adaptation of MΦ activation does occur in vivo, but that cellular plasticity is outweighed by functional capabilities specific to the tissue origin of the cell.