Some bacteria like Mycobacterium tuberculosis, the causative agent of tuberculosis, are intracellular pathogens. They invade and reside inside host cells, including those of the immune system, such as macrophages.
Inside the macrophage, the typical bacterial killing strategy does not go according to plan when dealing with intracellular bacteria. Some can aptly withstand the acidity. Some are capable of escaping from the phagosome. Some can hamper fusion of the phagosome with the lysosome. In these examples, as opposed to fostering a hostile environment, the phagosome becomes a home wherein bacteria may replicate without threat.
Within the macrophage, some phagolysosomes do successfully form and function, meaning some intracellular bacteria are killed and have associated peptides displayed on the macrophages MHCs, alongside surface-expressed CD40.
Overall, however, replication within innate immune cells like macrophages is an effective immune evasion strategy. It allows for the circumvention of the innate immune response. The macrophage will soon die and the intracellular bacteria is free to spread to other macrophages.
Help is required.
Dendritic cells are also at the site of infection. They phagocytose the bacteria, travel to the closest lymph node, and present pathogen-derived peptides on a MHC molecule. After being activated, T helper cells leave the lymph node for the infected macrophage.
With the help of two signals, macrophages become super-activated. The arriving T helper cells secrete a pro-inflammatory cytokine called interferon-gamma. As well, a molecule on the T cell (CD40L) binds CD40 on the macrophage.
Now super-activated, the macrophage begins to transcribe genes that lead to the production of compounds toxic to the bacteria. The fusion of phagosomes with lysosomes is improved, while the production of antimicrobial nitric oxide, reactive oxygen species, and proteases is increased.
Any intracellular invaders are killed.
This article’s content was created based upon the background accrued over the course of the author’s Honours BSc Degree in Microbiology & Immunology, which included Immunology, Virology, and Bacterial Pathogenesis course-work and exposure to topics from Janeway’s Immunobiology.
