Pathogens Can Regulate the Complement Pathway, Too!

Pathogens have evolved various strategies to manipulate the complement system, either by inhibiting complement cascades to evade immune attack or by exploiting the system to their advantage. Here are some examples of how pathogens manipulate the complement system:

Inhibition of Complement Cascades:

1. Decoy Molecules:
   • Some pathogens produce decoy molecules that mimic host cell surface proteins. These molecules can bind complement proteins, diverting them away from the pathogen and preventing complement activation. For example, some bacteria produce proteins that mimic human regulators of complement activation.
2. Cleavage and Inactivation:
   • Certain pathogens produce proteases that can cleave complement proteins, rendering them inactive. For instance, some bacterial proteases can cleave complement components like C3b, disrupting opsonization and phagocytosis.
3. Binding Complement Regulators:
   • Pathogens may express proteins that bind to complement regulators, such as factor H or CD59, preventing their proper function and inhibiting the formation of the membrane attack complex (MAC). Borrelia burgdorferi, the causative agent of Lyme disease, can bind factor H to evade complement-mediated lysis.
4. Inhibition of C5 Convertase:
   • Some pathogens can produce proteins that directly inhibit the formation or activity of the C5 convertase, preventing the cleavage of C5 and subsequent MAC formation. Streptococcus pyogenes produces the protein Streptococcal Inhibitor of Complement (SIC), which inhibits C5 convertase.

Exploiting the Complement System:

1. Surface Mimicry:
   • Some pathogens use surface molecules that mimic host cell structures to evade detection by the complement system. By resembling host cells, the pathogens avoid complement-mediated attack. Examples include Neisseria gonorrhoeae and Neisseria meningitidis.
2. Inhibition of Phagocytosis:
   • Pathogens may exploit the complement system to inhibit phagocytosis. Some bacteria, like Yersinia pestis, can resist phagocytosis by preventing the deposition of opsonins such as C3b on their surfaces.
3. Recruitment of Host Regulators:
   • Certain pathogens recruit host complement regulators to their surfaces, helping them evade complement attack. For example, Plasmodium falciparum, the causative agent of malaria, can incorporate host-derived complement regulators on its surface to protect against complement-mediated lysis.
4. Cleavage of Complement Components for Nutrient Acquisition:
   • Some pathogens, particularly parasites, may exploit complement components as a nutrient source. For instance, Leishmania parasites can cleave C3 and use the released fragments for nutritional purposes.

In summary, pathogens have evolved diverse mechanisms to manipulate the complement system, either by inhibiting its cascades to evade immune attack or by exploiting its components to their advantage for survival and proliferation. These strategies highlight the dynamic interplay between pathogens and the host immune system.

End of Section 2.1

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Source: ChatGPT response prompted and edited by Joel Graff.

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