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Phagocytosis of Legionella pneumophila is mediated by human monocyte complement receptors
1Department of Pediatrics, UCLA School of Medicine 90024.
Abstract:
We have examined receptors mediating phagocytosis of the intracellular bacterial pathogen, Legionella pneumophila. Three mAbs against the type 3 complement receptor (CR3), which recognizes C3bi, inhibit adherence of L. pneumophila to monocytes by 64 +/- 8% to 74 +/- 11%. An mAb against the type 1 complement receptor (CR1), which recognizes C3b, inhibits adherence by 68 +/- 1%. mAbs against other monocyte surface antigens do not significantly influence adherence. Monocytes plated on substrates of L. pneumophila membranes modulate their CR1 and CR3 receptors but not Fc receptors; such monocytes bind 70% fewer C3b-coated erythrocytes and 53% fewer C3bi-coated erythrocytes than control monocytes. Adherence of L. pneumophila to monocytes in nonimmune sera is dependent on heat-labile serum opsonins; adherence is markedly reduced in heat-inactivated serum (84% reduction) or buffer alone (97% reduction) compared with fresh serum. mAbs against CR1 and CR3 receptors also inhibit L. pneumophila intracellular multiplication and protect monocyte monolayers from destruction by this bacterium. This study demonstrates that human monocyte complement receptors, CR1 and CR3, mediate phagocytosis of L. pneumophila. These receptors may play a general role in mediating phagocytosis of intracellular pathogens.
Insights
Human monocyte complement receptors, complement receptor 1 (CR1) and complement receptor 3 (CR3), are key to phagocytosis of Legionella pneumophila. These receptors are vital for controlling intracellular bacterial infections.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Legionella pneumophila is an intracellular bacterial pathogen that infects monocytes.
- Phagocytosis is a critical immune process for clearing pathogens.
- The role of specific monocyte receptors in L. pneumophila phagocytosis remains to be fully elucidated.
Purpose of the Study:
- To investigate the specific monocyte receptors involved in the phagocytosis of Legionella pneumophila.
- To determine the role of complement receptors CR1 and CR3 in L. pneumophila adherence and intracellular multiplication.
Main Methods:
- Utilized monoclonal antibodies (mAbs) against complement receptors CR1 and CR3 to block receptor function.
- Assessed the effect of receptor blockade on L. pneumophila adherence to human monocytes.
- Investigated the impact of L. pneumophila membrane interaction on monocyte receptor expression.
- Evaluated the role of serum opsonins in L. pneumophila-monocyte interactions.
- Quantified the effect of CR1 and CR3 engagement on intracellular bacterial growth and monocyte survival.
Main Results:
- Monoclonal antibodies against CR1 and CR3 significantly inhibited L. pneumophila adherence to monocytes (64-74%).
- Monocytes exposed to L. pneumophila membranes showed reduced binding of C3b- and C3bi-coated erythrocytes, indicating receptor modulation.
- L. pneumophila adherence was dependent on heat-labile serum opsonins, with significantly reduced adherence in heat-inactivated serum or buffer.
- Blockade of CR1 and CR3 inhibited intracellular L. pneumophila multiplication and protected monocytes from bacterial-induced destruction.
Conclusions:
- Human monocyte complement receptors CR1 and CR3 are critical mediators of Legionella pneumophila phagocytosis.
- These complement receptors play a significant role in controlling intracellular bacterial infections.
- CR1 and CR3 may have a general role in the host defense against various intracellular pathogens.