Differences in uptake of mycobacteria by human monocytes: a role for complement

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Human peripheral blood monocytes (PBM) play a crucial role in the immune response to mycobacterial infections.
• The interaction between PBM and various mycobacterial species is influenced by serum factors, which can modulate phagocytosis.
• Understanding these interactions is vital for developing effective therapeutic strategies against mycobacterial diseases.

Purpose of the Study:

• To investigate the role of serum factors in the in vitro uptake of different mycobacterial species by human PBM.
• To elucidate the specific contribution of complement activation in mediating PBM-mycobacteria interactions.

Main Methods:

• Quantification of mycobacterial uptake by human PBM using flow cytometry.
• Assessment of serum factor influence by pre-incubating mycobacteria with normal, heat-inactivated, or complement-depleted serum.
• Evaluation of complement pathway involvement using EGTA and EDTA in conjunction with MgCl2.

Main Results:

• Mycobacterial species exhibited differential uptake by PBM, categorizing them into high-uptake (e.g., Mycobacterium avium complex, M. chelonae) and low-uptake groups (e.g., M. tuberculosis, M. kansasii).
• Serum complement significantly enhanced the uptake of M. avium complex by PBM, indicating complement-mediated phagocytosis.
• M. avium complex activated the alternative complement pathway and consumed significant hemolytic complement activity, while M. tuberculosis showed less serum dependence.

Conclusions:

• Serum factors, particularly complement, are critical for efficient in vitro uptake of Mycobacterium avium complex by human monocytes.
• The alternative complement pathway is involved in the serum-mediated uptake of M. avium complex.
• Serum's influence on PBM uptake is less pronounced for Mycobacterium tuberculosis compared to M. avium complex.