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

PLoS Pathogens

Dominik Rückerl¹  Sheelagh Duncan¹  Judith E. Allen¹  Tara E. Sutherland¹  Stephen J. Jenkins¹  Lucy H. Jackson-Jones²  Tom A. Barr³  Sharon M. Campbell⁴  James P. Hewitson⁴  Rick M. Maizels⁵ 

[1] Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom;Centre for Immunology and Infection, University of York, York, United Kingdom;Centre for Inflammation Research, School of Clinical Sciences, University of Edinburgh, Edinburgh, United Kingdom;Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom;Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom

关键词: Co-infections;    Nematode infections;    Helminth infections;    Macrophages;    Monocytes;    Antibacterials;    Blood;    Gene expression;   

DOI  :  10.1371/journal.ppat.1006233

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY