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Immunoglobulin M-dependent classical complement pathway activation in killing of Pentatrichomonas hominis
1Department of Parasitology and Tropical Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Abstract:
Complement pathway activity in the killing of Pentatrichomonas hominis was investigated in this study. At 10(5) organisms per ml, P. hominis was completely killed by the presence of 1% normal human serum. In contrast, no killing effect on P. hominis was observed when specific antibodies were absorbed or when the complement was destroyed. Moreover, Mg2+-ethylene glycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-treated serum had no killing effect on P. hominis, while serum heated at 50 degrees C or treated with zymosan killed P. hominis as well as did normal human serum. Further study using gel filtration (Sephacryl S-300) and affinity chromatography (protein A) revealed that immunoglobulin M (IgM; 20 micrograms/ml) alone was responsible for the complement activation in the killing of P. hominis, but both IgA (24 micrograms/ml) and IgG (180 micrograms/ml) had no effect on complement-mediated lysis. On the other hand, IgG at 1,260 micrograms/ml completely inhibited complement-mediated killing by IgM, suggesting that a blocking factor is present in IgG. The results of this study indicate that a mechanism of IgM-dependent classical complement pathway activation contributes to the killing effect of normal human serum on P. hominis.
Insights
Normal human serum kills Pentatrichomonas hominis via the complement system. Immunoglobulin M (IgM) alone activates complement, while IgG may block this process, indicating a novel IgM-dependent pathway.
Area of Science:
- Immunology
- Parasitology
- Microbiology
Background:
- Pentatrichomonas hominis is a protozoan parasite.
- The human complement system is crucial for innate immunity.
- Mechanisms of complement-mediated parasite killing are not fully understood.
Purpose of the Study:
- To investigate the role of the complement pathway in Pentatrichomonas hominis killing.
- To identify the specific components of normal human serum responsible for P. hominis lysis.
Main Methods:
- Serum treatment experiments (antibody absorption, complement destruction, heat inactivation, zymosan treatment).
- Analysis of complement activation using gel filtration and affinity chromatography.
- Quantification of immunoglobulin activity (IgM, IgA, IgG).
Main Results:
- Normal human serum (1% concentration) effectively killed P. hominis.
- Complement destruction or antibody absorption abrogated the killing effect.
- Immunoglobulin M (IgM) alone mediated complement activation and parasite killing.
- High concentrations of Immunoglobulin G (IgG) inhibited IgM-mediated killing, suggesting a blocking effect.
Conclusions:
- The classical complement pathway, activated by IgM, is a key mechanism for killing Pentatrichomonas hominis.
- Immunoglobulin M plays a critical role in complement-dependent lysis of P. hominis.
- Immunoglobulin G may possess a regulatory or inhibitory function in this immune response.