Macrophage origin limits functional plasticity in helminth-bacterial co-infection.
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.
Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.|Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
Dominik
0000-0002-0206-1451
D
Rückerl
Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Sharon M
SM
Campbell
Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Sheelagh
S
Duncan
Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.|Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
Tara E
0000-0001-9334-8206
TE
Sutherland
Centre for Inflammation Research, School of Clinical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Stephen J
0000-0002-0233-5424
SJ
Jenkins
Centre for Immunology and Infection, University of York, York, United Kingdom.
James P
JP
Hewitson
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
Tom A
TA
Barr
Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.|Centre for Cardiovascular Science, School of Clinical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Lucy H
LH
Jackson-Jones
Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Rick M
RM
Maizels
Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.|Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
Judith E
0000-0002-3829-066X
JE
Allen
D000818:Animals; D060085:Coinfection; D005434:Flow Cytometry; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009351:Nematospiroides dubius / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000382:microbiology*; D012485:Salmonella typhi / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology / Q000382:microbiology*