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Published on: May 19, 2020
Serum amyloid A is an innate immune opsonin for Gram-negative bacteria
Chandrabala Shah1, Ranjeeta Hari-Dass, John G Raynes
1Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St, London WCIE 7HT, United Kingdom.
Abstract:
Serum amyloid A (SAA) is the major acute-phase protein in man and most mammals. Recently we demonstrated that SAA binds to many Gram-negative bacteria including Escherichia coli and Pseudomonas aeruginosa through outer membrane protein A (OmpA) family members. Therefore we investigated whether SAA altered the response of innate phagocytic cells to bacteria. Both the percentage of neutrophils containing E coli and the number of bacteria per neutrophil were greatly increased by SAA opsonization, equivalent to the increase seen for serum opsonization. In contrast, no change was seen for Streptococcus pneumoniae, a bacteria that did not bind SAA. Neutrophil reactive oxygen intermediate production in response to bacteria was also increased by opsonization with SAA. SAA opsonization also increased phagocytosis of E coli by peripheral blood mononuclear cell-derived macrophages. These macrophages showed strong enhancement of TNF-alpha and IL-10 production in response to SAA-opsonized E coli and P aeruginosa. SAA did not enhance responses in the presence of bacteria to which it did not bind. These effects of SAA occur at normal concentrations consistent with SAA binding properties and a role in innate recognition. SAA therefore represents a novel innate recognition protein for Gram-negative bacteria.
Insights
Serum amyloid A (SAA) enhances the innate immune system's ability to recognize and clear Gram-negative bacteria. SAA opsonization significantly boosts neutrophil and macrophage responses to bacteria like E. coli and P. aeruginosa.
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Serum amyloid A (SAA) is a major acute-phase protein in mammals.
- Previous research showed SAA binds to Gram-negative bacteria via outer membrane protein A (OmpA).
Purpose of the Study:
- To investigate if SAA influences the response of innate phagocytic cells to bacteria.
- To determine SAA's role in innate immune recognition of bacterial pathogens.
Main Methods:
- Assessing neutrophil phagocytosis and reactive oxygen intermediate production with SAA-opsonized bacteria.
- Evaluating macrophage phagocytosis and cytokine (TNF-alpha, IL-10) production.
- Comparing responses to SAA-binding (E. coli, P. aeruginosa) versus non-binding (S. pneumoniae) bacteria.
Main Results:
- SAA opsonization significantly increased neutrophil phagocytosis of E. coli, comparable to serum opsonization.
- SAA enhanced neutrophil reactive oxygen intermediate production.
- SAA opsonization increased macrophage phagocytosis of E. coli and boosted TNF-alpha and IL-10 production in response to SAA-opsonized Gram-negative bacteria.
- No enhancement was observed with S. pneumoniae, which does not bind SAA.
Conclusions:
- SAA acts as a novel innate recognition protein for Gram-negative bacteria.
- SAA significantly enhances the phagocytic cell response to Gram-negative bacteria at physiological concentrations.
- SAA plays a crucial role in the innate immune system's defense against Gram-negative infections.
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