CD40-CD154 interactions between macrophages and natural killer cells during sepsis are critical for macrophage activation and are not interferon gamma dependent.
Open accessAbstract
Natural killer (NK) cell interactions with macrophages have been shown to be important during bacterial sepsis in activating macrophages to improve bacterial clearance. The mechanism for this increased activation, however, is unclear. This study determines the relative roles of interferon (IFN)-gamma and CD40/CD154 direct cell interactions on macrophage and NK cell activation in an experimental model of sepsis. Splenic NK cells and peritoneal macrophages were isolated and cultured alone or in coculture, with and without LPS. CD69 expression on NK cells, phagocytosis ability of macrophages, and cell cytokine production was assessed at 24 and 48 h. Coculture of NK cells and macrophages significantly increased activation levels of both cell types, and through experiments culturing NK cells with supernatants from stimulated macrophages and macrophages with supernatants from stimulated NK cells, this activation was determined to be cell-contact-dependent. Similar experiments were conducted using NK cells from IFN-gamma deficient (-/-) mice, as well as anti-IFN-gamma neutralizing antibody. These experiments determined that IFN-gamma is not required for NK or macrophage activation, although it did augment activation levels. Experiments were again repeated using peritoneal macrophages from CD40-/- mice or splenic NK cells from CD154-/- mice. CD40/CD154 interactions were important in the ingestion of bacteria by macrophages, but did not affect NK cell activation at 24 h. There was, however, a protective effect of CD40/CD154 interactions on NK cell activation-induced cell death that occurred at 48 h. CD40/CD154 interactions between macrophages and NK cells are therefore important in macrophage phagocytosis, and are not dependent on IFN-gamma.
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IFNγ increases macrophage activation during innate immunity.
“They increase macrophage activation during innate immunity (Scott et al., 2004)”
From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Scott et al., 2004
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Secondary bacterial infections associated with influenza pandemics
Morris, D. E., Cleary, D. W., & Clarke, S. C. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01041 · Cited by 576 · see citing works
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- Authors
- SCOTT, M. J., HOTH, J. J., STAGNER, M. K., GARDNER, S. A., PEYTON, J. C., & CHEADLE, W. G.
- Affiliations
- University of Pittsburgh (US)
- Wake Forest University (US)
- Veterans Health Administration (US)
- University of Louisville (US)
- Corresponding author
- CHEADLE, W G
- ORCID
- Venue
- Clinical and Experimental Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-07-23
- Volume
- 137
- Issue
- 3
- Pages
- 469-477
- ISSN
- 0009-9104 (ISSN-L)
- 1365-2249
- PMC
- PMC1809143
- OpenAlex
- W2083782421
- Cited by
- 53
- References
- 30
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2022: 1 · 2021: 3 · 2019: 2 · 2017: 5 · 2014: 4 · 2013: 7 · 2012: 1
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical & Experimental Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Office of Research and Development
- National Institute of Biomedical Imaging and Bioengineering (R01EB002004)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- CD40-CD154 interaction, macrophage activation, natural killer cells, sepsis, interferon-gamma, phagocytosis, bacterial clearance, lipopolysaccharide
- MeSH terms
- CD69 Antigens, Animals, Antigens, Differentiation, T-Lymphocyte, Cell Communication, Cells, Cultured, Interferon-gamma, Killer Cells, Natural, Lipopolysaccharides, Macrophage Activation, Mice, Inbred C57BL, Antigens, CD, Cytokines, Macrophages, Peritoneal, Mice, Knockout, Sepsis, CD40 Antigens, CD40 Ligand, Models, Animal, Lectins, C-Type, Mice
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