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

Rückerl, Dominik and Campbell, Sharon M and Duncan, Sheelagh and Sutherland, Tara E and Jenkins, Stephen J and Hewitson, James P and Barr, Tom A and Jackson-Jones, Lucy H and Maizels, Rick M and Allen, Judith E (2017) Macrophage origin limits functional plasticity in helminth-bacterial co-infection. PLoS Pathogens, 13 (3). ISSN 1553-7366

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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.

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Journal Article
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PLoS Pathogens
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09 May 2018 14:16
Last Modified:
22 Nov 2022 05:48