Bacterial Mechanisms of Immune Evasion

By Dillon Lim - Medicine Student @ Brasenose College, Oxford


Many common human pathogens are bacteria: prokaryotic cells characterised by their circular chromosome and peptidoglycan cell walls, among other features. Bacterial pathogens have co-evolved with their human hosts over millennia, such that just as we have evolved many ways to fight off bacterial infection, bacteria have evolved many ways to escape our immune system. We’ll look at just some of the common ways in this article.

Molecular mimicry is a term used to describe the way that some bacteria express molecules on their surface which are very similar to host-expressed molecules. These are the same molecules that an immune cell might use to determine the identity of a cell as “self” or “non-self” – so mimicry confuses the immune cell into thinking a bacterial cell is in fact a human cell instead. Some types of Campylobacter have short oligosaccharide chains that look like human structures called gangliosides. The most well-known type of sorting blood group is the ABO system, but other systems exist, including sorting by Lewis antigen. H. pylori, a bacterium that colonises the stomach, has structures that mimic these antigens.

Antibodies are of course an important way we target bacteria. They opsonise bacteria (facilitating phagocytosis by immune cells), sequester bacterial products, and can mediate lysis of bacterial cells. Some bacteria produce enzymes which break down antibodies. IgA is an important antibody at mucosal linings – like in the respiratory or digestive tracts. The IgA proteases produced by Neisseria meningitidis and Staphylococcus pneumoniae allow their colonisation of the upper respiratory tracts. Streptococcus pyogenes produces two proteins that target antibodies: IgG degrading enzyme and exotoxin B. Staphylococcus aureus has an interesting strategy that doesn’t involve degradation – it binds the antibody with its SpA protein, but at the opposite end (what we call the Fc fragment) to the bit of the antibody which normally binds bacteria (the Fab fragment). Crucially, the Fc fragment is what the immune system needs to recognise that the antibody has successfully bound a bacterium – so if the bacterium itself has bound it, the antibody can’t carry out the functions that we described above properly.

Some bacteria have ways to avoid being killed by immune cells after they are phagocytosed. Mycobacterium tuberculosis is able to continue multiplying in macrophages, which we think is something to do with the molecule trehalose dimycolate (TDM). When TDM is experimentally removed from these bacteria the rates of successful phagocytosis increase significantly, but drop back down once we add it back in. Species of Shigella secrete a protein called IpaB, which not only prevents their digestion by macrophages but actually induces pyroptosis in macrophages – a special form of cell death that occurs in inflammation.

Finally, we’ll talk about inhibition of complement proteins. These are a group of immune mediators that are particularly important for our antibacterial defences. S. aureus produces proteins like SSL5 and CHIPS that inhibit complement signals used to activate immune cells. To prevent complement-mediated damage on our own cells, we produce proteins like Factor H, which breaks down complement. N. meningitidis has a Factor H binding protein, which recruits Factor H to its own membranes for protection.

Further reading:

  1. Microbial Ninja Warriors: Bacterial Immune Evasion.

  2. Pathogens have evolved various means of evading or subverting normal host defenses.

  3. Neutrophils and Bacterial Immune Evasion. (advanced)

  4. Anti-Immunology: Evasion of the Host Immune System by Bacterial and Viral Pathogens. (advanced)