The mannose cap of mycobacterial lipoarabinomannan does not dominate the Mycobacterium-host interaction

Area of Science:

• Microbiology
• Immunology
• Molecular Biology

Background:

• Pathogenic mycobacteria survive within host cells by suppressing immune responses.
• Lipoarabinomannan (LAM), a glycolipid, and its mannose cap are thought to inhibit phagolysosome fusion and promote IL-10 production, crucial for mycobacterial virulence.

Purpose of the Study:

• To investigate the role of the mannose cap of LAM in mycobacterial virulence using live bacteria.
• To challenge the existing paradigm that the mannose cap is a dominant factor in Mycobacterium-host interactions.

Main Methods:

• Generated capless mutants of Mycobacterium marinum and Mycobacterium bovis BCG by inactivating Rv1635c homologues.
• Assessed bacterial uptake, phagolysosome fusion, and survival in vitro and in vivo (zebrafish, mice).
• Evaluated binding to dendritic cells and DC-SIGN, and IL-10 induction in response to capless mutants.

Main Results:

• Capless M. marinum showed slightly altered macrophage interactions but maintained bacterial survival in vitro and in vivo.
• Capless M. bovis BCG exhibited variable binding to dendritic cells and DC-SIGN but no change in IL-10 induction.
• Capless M. bovis BCG demonstrated similar survival and cytokine profiles in mice compared to the parent strain.

Conclusions:

• The mannose cap of LAM is not a dominant factor in Mycobacterium-host interactions.
• The current paradigm regarding the critical role of mannose-capped LAM in virulence is challenged by these findings.
• Further research is needed to understand the complex mechanisms of mycobacterial persistence and immune evasion.