Interaction of Legionella micdadei with human monocytes
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Abstract:
We have recently shown that Legionella micdadei is ingested, but not killed, by human neutrophils. Herein we investigate the role of human monocytes in defense against this organism. Serum and monocytes from normal donors having no detectable antibody to L. micdadei were used. Egg-passaged L. micdadei organisms multiplied inside these monocytes with a peak growth of 2 log units within 12 h. No growth occurred when monocytes were omitted or when sonicated monocytes were used. Electron microscopy 18 h after infection revealed these organisms to be intracellular in normal-appearing phagosomes. When the input multiplicity of L. micdadei was greater than 1 CFU per monocyte, no intracellular growth occurred. When egg-passaged Legionella pneumophila organisms were used, intracellular organisms were found in phagosomes studded with ribosomes at the same time period. Peak intracellular growth of L. pneumophilia occurred by 48 h. L. micdadei activated the complement system and was opsonized by C3. However the use of complement-depleted (heat-inactivated) serum as the opsonic source had no effect on the bacterium's ingestion or growth in the monocyte. Thus, L. micdadei multiples in human monocytes. This entry and growth is independent of antibody or complement. The intracellular locations of L. micdadei and L. pneumophila differ, suggesting different mechanisms for the survival of these two organisms in the monocyte.
Insights
Legionella micdadei multiplies within human monocytes, evading immune defenses. This intracellular growth is independent of antibodies or complement, highlighting a novel survival mechanism for this bacterium.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Legionella micdadei is known to be ingested but not killed by human neutrophils.
- The role of human monocytes in the immune response against L. micdadei remains to be fully elucidated.
Purpose of the Study:
- To investigate the interaction between Legionella micdadei and human monocytes.
- To determine the mechanisms of L. micdadei survival and replication within monocytes.
Main Methods:
- Human monocytes were infected with egg-passaged L. micdadei.
- Bacterial growth was assessed using colony-forming units (CFUs) over time.
- Electron microscopy was used to visualize intracellular bacteria.
- Complement activation and opsonization were evaluated using complement-depleted serum.
Main Results:
- L. micdadei multiplied within human monocytes, with peak growth observed at 12 hours.
- Intracellular replication was dependent on viable monocytes.
- Bacteria resided in normal-appearing phagosomes.
- L. micdadei entry and growth were independent of antibody and complement.
- Compared to Legionella pneumophila, L. micdadei showed distinct intracellular localization and replication kinetics.
Conclusions:
- Human monocytes support the intracellular multiplication of Legionella micdadei.
- The bacterium employs mechanisms for survival and replication within monocytes that are independent of antibody and complement-mediated immunity.
- Differential intracellular localization suggests distinct host-pathogen interaction strategies between L. micdadei and L. pneumophila within monocytes.