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Published on: February 22, 2019
Mitogenic component in polar lipid-enriched Anaplasma phagocytophilum membranes
Kyoung-Seong Choi1, J Stephen Dumler
1College of Life Sciences and Natural Resources, Department of Animal Science, Sangju National University, Sangju 742-711, Korea.
Abstract:
Human granulocytic anaplasmosis is an emerging tick-borne disease caused by Anaplasma phagocytophilum. A. phagocytophilum cells activate Toll-like receptor 2 signaling and possess mitogenic activity, and A. phagocytophilum infection in vivo activates NKT cells unrelated to major surface protein 2 (Msp2) hypervariable region expression. Thus, we hypothesized that lipoprotein or glycolipid components of A. phagocytophilum membranes could be important triggers of the innate immune response and immunopathology. A. phagocytophilum membranes depleted of Msp2 and protein antigens enhanced the proliferation of naïve mouse splenocytes beyond that of untreated membranes. Protein-depleted and polar lipid-enriched membranes from low-passage A. phagocytophilum cultures enhanced naïve splenocyte lymphoproliferation to a much greater degree than did these fractions from high-passage cultures of bacterial membranes (1.8- to 3.7-fold for protein-depleted fractions and 4.8- to > or =17.7-fold for polar lipid-enriched fractions). These results support the hypothesis that components that are enriched among polar lipids in the A. phagocytophilum membrane stimulate innate immune cell proliferation, possibly activating NKT cells that link innate and adaptive immunity, and immunopathology.
Insights
Components within Anaplasma phagocytophilum membranes stimulate innate immune cell proliferation. Polar lipids, particularly from low-passage bacteria, significantly enhance splenocyte lymphoproliferation, suggesting a role in immune response.
Area of Science:
- Immunology
- Microbiology
- Tick-borne diseases
Background:
- Human granulocytic anaplasmosis is an emerging tick-borne disease caused by Anaplasma phagocytophilum.
- A. phagocytophilum activates Toll-like receptor 2 signaling and NKT cells.
- The role of membrane components in innate immune activation is unclear.
Purpose of the Study:
- To investigate the role of A. phagocytophilum membrane components in innate immune response.
- To determine if lipoprotein or glycolipid components trigger immune response and immunopathology.
- To compare the mitogenic activity of membrane fractions from different bacterial passages.
Main Methods:
- Preparation of A. phagocytophilum membrane fractions depleted of Msp2 and protein antigens.
- Treatment of naïve mouse splenocytes with membrane fractions.
- Assessment of splenocyte proliferation and lymphoproliferation.
Main Results:
- Membranes depleted of Msp2 and protein antigens enhanced splenocyte proliferation compared to untreated membranes.
- Protein-depleted and polar lipid-enriched membranes from low-passage A. phagocytophilum showed significantly greater lymphoproliferation (4.8- to > or =17.7-fold) than those from high-passage cultures.
- Polar lipid-enriched fractions demonstrated the highest mitogenic activity.
Conclusions:
- Components enriched in A. phagocytophilum polar lipids stimulate innate immune cell proliferation.
- These findings support the hypothesis that membrane lipids are key triggers of the innate immune response.
- The results suggest a potential role for NKT cell activation by these lipid components, linking innate and adaptive immunity and contributing to immunopathology.
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