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PMID: 22749354 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

NK cell-derived interferon-γ orchestrates cellular dynamics and the differentiation of monocytes into dendritic cells at the site of infection.

Immunity ·Vol. 36 ·No. 6 ·2012-06-29 ·Pages 1047-59

Goldszmid RS, Caspar P, Rivollier A, White S, Dzutsev A, Hieny S, Kelsall B, Trinchieri G, Sher A

Abstract

Dendritic cells (DCs), monocytes, and/or macrophages initiate host-protective immune responses to intracellular pathogens in part through interleukin-12 (IL-12) production, although the relative contribution of tissue resident versus recruited cells has been unclear. Here, we showed that after intraperitoneal infection with Toxoplasma gondii cysts, resident mononuclear phagocytes are replaced by circulating monocytes that differentiate in situ into inflammatory DCs (moDCs) and F4/80(+) macrophages. Importantly, NK cell-derived interferon-γ (IFN-γ) was required for both the loss of resident mononuclear phagocytes and the local differentiation of monocytes into macrophages and moDCs. This newly generated moDC population and not the resident DCs (or macrophages) served as the major source of IL-12 at the site of infection. Thus, NK cell-derived IFN-γ is important in both regulating inflammatory cell dynamics and in driving the local differentiation of monocytes into the cells required for initiating the immune response to an important intracellular pathogen.

MeSH Terms
Adoptive Transfer Animals Antigens, Ly/analysis Cell Differentiation Chemotaxis, Leukocyte Dendritic Cells/immunology,pathology,transplantation Genes, Reporter Interferon-gamma/physiology Interleukin-12 Subunit p40/biosynthesis,genetics Killer Cells, Natural/immunology,metabolism Macrophages, Peritoneal/immunology,transplantation Mice Mice, Inbred BALB C Mice, Inbred C57BL Monocytes/chemistry,immunology,pathology,transplantation Myeloid Differentiation Factor 88/physiology Neutrophils/immunology Peritonitis/immunology,parasitology Phagocytes/classification,immunology,pathology Receptors, Interferon/deficiency,physiology Recombinant Fusion Proteins/biosynthesis,genetics Specific Pathogen-Free Organisms T-Lymphocyte Subsets/immunology Toxoplasmosis, Animal/immunology
Chemicals
Antigens, Ly Interleukin-12 Subunit p40 Ly-6C antigen, mouse Myd88 protein, mouse Myeloid Differentiation Factor 88 Receptors, Interferon Recombinant Fusion Proteins interferon gamma receptor Interferon-gamma
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Goldszmid Romina S
Laboratory of Experimental Immunology, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA. rgoldszmid@mail.nih.gov
Caspar Pat
Rivollier Aymeric
White Sandy
Dzutsev Amiran
Hieny Sara
Kelsall Brian
Trinchieri Giorgio
Sher Alan
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2012.03.026
Email
rgoldszmid@mail.nih.gov
Published
2012-06-29
Pages
1047-59
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC3412151
Subset
IM
Grants
Intramural NIH HHS · Z99 CA999999 · United States
Corrections
CommentIn
PMID: 22749350
External Links
PubMed source DOI: 10.1016/j.immuni.2012.03.026 PMC Full Text View journal details
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