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Published on: February 23, 2021
Gram-positive and Gram-negative bacteria elicit different patterns of pro-inflammatory cytokines in human monocytes
Christina C Hessle1, Bengt Andersson, Agnes E Wold
1Department of Clinical Bacteriology, Göteborg University, Guldhedsgatan 10, SE-413 46 Göteborg, Sweden. christina.hessle@microbio.gu.se
Abstract:
Pro-inflammatory cytokines secreted by tissue macrophages recruit polymorphonuclear leukocytes and evoke fever, cachexia and production of acute phase proteins. This study investigates whether Gram-positive and Gram-negative bacteria equally and efficiently trigger production of the pro-inflammatory cytokines IL-1 beta, IL-6, IL-8 and TNF-alpha in human monocytes. A range of aerobic and anaerobic Gram-positive and Gram-negative bacteria were killed by UV-light and added in different concentrations to human monocytes. Cytokines were measured in 24 h supernatants by ELISA. Gram-positive and Gram-negative bacteria were equally efficient inducers of IL-1 beta, but Gram-positive bacteria generated twice as much TNF-alpha as did Gram-negative bacteria (p<0.001 for 25 and 250 bacteria/cell). In contrast, Gram-negative bacteria induced at least twice as much IL-6 and IL-8 as did Gram-positive bacteria (p<0.001 for 2.5, 25 and 250 bacteria/cell). While the cytokine responses to LPS were similar to those induced by the corresponding amount of Gram-negative bacteria, the strong IL-1 beta and TNF-alpha responses to Gram-positive bacteria could not be induced by soluble peptidoglycan or lipotheicoic acid. The particular nature of the bacteria, thus seem to modify the response to Gram-positive bacterial components. The different cytokine profiles evoked by Gram-positive and Gram-negative bacteria might optimize clearance of bacteria that differ in cell wall structure.
Insights
Gram-positive and Gram-negative bacteria differentially stimulate human monocytes to produce pro-inflammatory cytokines. These distinct cytokine profiles, including Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), and Tumor Necrosis Factor-alpha (TNF-α), may aid in clearing bacteria with varying cell wall structures.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Pro-inflammatory cytokines from macrophages orchestrate immune responses, including fever and acute phase protein production.
- Understanding differential bacterial induction of cytokines is crucial for immune response modulation.
Purpose of the Study:
- To investigate if Gram-positive and Gram-negative bacteria equally trigger the production of IL-1β, IL-6, IL-8, and TNF-α in human monocytes.
- To compare the efficiency of different bacterial types in stimulating specific cytokine responses.
Main Methods:
- Human monocytes were exposed to UV-killed Gram-positive and Gram-negative bacteria at various concentrations.
- Cytokine levels (IL-1β, IL-6, IL-8, TNF-α) in supernatants were quantified using ELISA after 24 hours.
- Responses to bacterial components like LPS, peptidoglycan, and lipoteichoic acid were assessed.
Main Results:
- Both bacterial types were equally effective in inducing IL-1β.
- Gram-positive bacteria induced twice as much TNF-α compared to Gram-negative bacteria.
- Gram-negative bacteria induced at least twice as much IL-6 and IL-8 as Gram-positive bacteria.
- Bacterial components like peptidoglycan and lipoteichoic acid did not fully replicate the IL-1β and TNF-α responses seen with whole Gram-positive bacteria.
Conclusions:
- The type of bacteria significantly influences the profile of pro-inflammatory cytokines produced by human monocytes.
- Distinct cytokine profiles elicited by Gram-positive and Gram-negative bacteria may represent an evolutionary adaptation for optimizing pathogen clearance based on cell wall composition.
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