Involvement of Antilipoarabinomannan Antibodies in Classical Complement Activation in Tuberculosis

AUTOR(ES)

Hetland, Geir

FONTE

American Society for Microbiology

RESUMO

We examined alternative and classical complement activation induced by whole bacilli of Mycobacterium bovis BCG and Mycobacterium tuberculosis products. After exposure to BCG, there were higher levels of the terminal complement complex in sera from Indian tuberculosis patients than in sera from healthy controls. The addition of BCG with or without EGTA to these sera indicated that approximately 70 to 85% of the total levels of the terminal complement complex was formed by classical activation. Sera from Indian tuberculosis patients contained more antibody to lipoarabinomannan (LAM) than sera from healthy Indians. Levels of anti-LAM immunoglobulin G2 (IgG2), but not anti-LAM IgM, correlated positively with classical activation induced by BCG in the sera. By flow cytometry, deposition of C3 and terminal complement complex on bacilli incubated with normal human serum was demonstrated. The anticomplement staining was significantly reduced in the presence of EGTA and EDTA. Flow cytometry also revealed the binding of complement to BCG incubated with rabbit anti-LAM and then with factor B-depleted serum. This indicates that classical activation plays a major role in complement activation induced by mycobacteria and that anti-LAM IgG on the bacilli can mediate this response. Classical complement activation may be important for the extent of phagocytosis of M. tuberculosis by mononuclear phagocytes, which may influence the course after infection.

Documentos Relacionados

• Complement activation by isolated myelin: activation of the classical pathway in the absence of myelin-specific antibodies.
• Classical complement pathway activation by antipneumococcal antibodies leads to covalent binding of C3b to antibody molecules.
• Classical and alternative complement pathway activation by pneumococci.
• Immunoglobulin M-dependent classical complement pathway activation in killing of Pentatrichomonas hominis.
• Role of the Classical Pathway of Complement Activation in Experimentally Induced Polymicrobial Peritonitis