Bacteria- and fungus-derived PAMPs induce innate immune memory via similar functional, metabolic, and transcriptional adaptations
© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
Exposure to pathogen-associated molecular patterns (PAMPs) induces an augmented, broad-spectrum antimicrobial response to subsequent infection, a phenomenon termed innate immune memory. This study examined the effects of treatment with β-glucan, a fungus-derived dectin-1 ligand, or monophosphoryl lipid A (MPLA), a bacteria-derived Toll-like receptor 4 ligand, on innate immune memory with a focus on identifying common cellular and molecular pathways activated by these diverse PAMPs. Treatment with either PAMP prepared the innate immune system to respond more robustly to Pseudomonas aeruginosa infection in vivo by facilitating mobilization of innate leukocytes into blood, recruitment of leukocytes to the site of infection, augmentation of microbial clearance, and attenuation of cytokine production. Examination of macrophages ex vivo showed amplification of metabolism, phagocytosis, and respiratory burst after treatment with either agent, although MPLA more robustly augmented these activities and more effectively facilitated killing of bacteria. Both agents activated gene expression pathways in macrophages that control inflammation, antimicrobial functions, and protein synthesis and suppressed pathways regulating cell division. β-glucan treatment minimally altered macrophage differential gene expression in response to lipopolysaccharide (LPS) challenge, whereas MPLA attenuated the magnitude of the LPS-induced transcriptional response, especially cytokine gene expression. These results show that β-glucan and MPLA similarly augment the innate response to infection in vivo. Yet, MPLA more potently induces alterations in macrophage metabolism, antimicrobial functions, gene transcription and the response to LPS.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:115 |
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| Enthalten in: |
Journal of leukocyte biology - 115(2024), 2 vom: 19. Jan., Seite 358-373 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
McBride, Margaret A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.01.2024 Date Revised 20.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/jleuko/qiad120 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Bacteria- and fungus-derived PAMPs induce innate immune memory via similar functional, metabolic, and transcriptional adaptations |
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| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a Exposure to pathogen-associated molecular patterns (PAMPs) induces an augmented, broad-spectrum antimicrobial response to subsequent infection, a phenomenon termed innate immune memory. This study examined the effects of treatment with β-glucan, a fungus-derived dectin-1 ligand, or monophosphoryl lipid A (MPLA), a bacteria-derived Toll-like receptor 4 ligand, on innate immune memory with a focus on identifying common cellular and molecular pathways activated by these diverse PAMPs. Treatment with either PAMP prepared the innate immune system to respond more robustly to Pseudomonas aeruginosa infection in vivo by facilitating mobilization of innate leukocytes into blood, recruitment of leukocytes to the site of infection, augmentation of microbial clearance, and attenuation of cytokine production. Examination of macrophages ex vivo showed amplification of metabolism, phagocytosis, and respiratory burst after treatment with either agent, although MPLA more robustly augmented these activities and more effectively facilitated killing of bacteria. Both agents activated gene expression pathways in macrophages that control inflammation, antimicrobial functions, and protein synthesis and suppressed pathways regulating cell division. β-glucan treatment minimally altered macrophage differential gene expression in response to lipopolysaccharide (LPS) challenge, whereas MPLA attenuated the magnitude of the LPS-induced transcriptional response, especially cytokine gene expression. These results show that β-glucan and MPLA similarly augment the innate response to infection in vivo. Yet, MPLA more potently induces alterations in macrophage metabolism, antimicrobial functions, gene transcription and the response to LPS | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
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| 650 | 4 | |a monophosphoryl lipid A | |
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| 700 | 1 | |a Stothers, Cody L |e verfasserin |4 aut | |
| 700 | 1 | |a Fensterheim, Benjamin A |e verfasserin |4 aut | |
| 700 | 1 | |a Caja, Katherine R |e verfasserin |4 aut | |
| 700 | 1 | |a Owen, Allison M |e verfasserin |4 aut | |
| 700 | 1 | |a Hernandez, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Bohannon, Julia K |e verfasserin |4 aut | |
| 700 | 1 | |a Patil, Naeem K |e verfasserin |4 aut | |
| 700 | 1 | |a Ali, Sabah |e verfasserin |4 aut | |
| 700 | 1 | |a Dalal, Sujata |e verfasserin |4 aut | |
| 700 | 1 | |a Rahim, Mohsin |e verfasserin |4 aut | |
| 700 | 1 | |a Trenary, Irina A |e verfasserin |4 aut | |
| 700 | 1 | |a Young, Jamey D |e verfasserin |4 aut | |
| 700 | 1 | |a Williams, David L |e verfasserin |4 aut | |
| 700 | 1 | |a Sherwood, Edward R |e verfasserin |4 aut | |
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