Pathogen Refuges: What are they?

Pathogens can hide in areas of the body that are not well-protected by the immune system. As they are also generally areas with poor or indirect blood circulation, they can be difficult to reach with pharmaceutical interventions like antibiotics.

There are two kinds of pathogen refuges. One kind is called “immune privileged sites.” These are parts of the body that are important and uniquely susceptible to damage from inflammatory immune processes. Consequently, they have evolved to be protected from the immune system. These include parts of the reproductive system, the eyes and the central nervous system. Usually when a cell is infected the immune system has various ways of interacting with the cell to prevent the infection from spreading to other cells, including destruction of the cell. Immune privileged cells have proteins on their surface that interfere with interactions between the immune system and the cell

Another kind of pathogen refuge are areas with poor circulation, where the immune system cannot quickly respond. These areas include cartilage and joint fluid.

A few examples of pathogens that take advantage of these areas include:

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Ebola

Because new outbreaks can be so devastating, Ebola is one of the better studied examples of a pathogen that finds refuge in the body. Two notable areas of refuge for Ebola are the eyes and the testes.

One in four people who have recovered from Ebola have long-term eye symptoms that may indicate ongoing viral infection inside the eye. One study found that about one in four of those people (so one in 16 survivors) had cellular responses that suggested particularly low immune protection of the eye. Dr. Ian Crozier, who was treated for Ebola at Emory Hospital in Atlanta, famously developed eye problems several months after his recovery from a viral load in his eye that turned out to be higher than what had been found in his blood at the peak of his illness.

A recent case of a strain of Ebola becoming active in a community five years after an outbreak brings up known cases of transmission from semen after a long time. The testes are protected from the immune system and are another place where pathogens can hang out.

Shingles

Shingles is a reactivation of varicella-zoster virus, the virus that causes chicken pox. As with other herpes viruses (there are nine that are known to infect humans), infections can disappear for long periods of time before reappearing. The virus hides in nerve cells that are immune privileged. When it comes out, it has additional tricks to stop the complement immune system from attacking the cells it invades, allowing it to extend its time to reach the skin and spread the virus.

Lyme Borreliosis

Borrelia burgdorferi, the bacteria that causes Lyme disease, can cause severe arthritis that sometimes does not respond well to antibiotics. In these cases the bacteria, alive or dead, is found in synovial fluid (joint fluid) and cartilage. While a lot is unknown, researchers theorize that the delayed opportunity for an immune response leads to a hyper immune reaction. This delay is due to the combination of the refuge opportunity and immune suppression caused by the bacteria. Even if the infection is successfully treated, bacterial proteins from dead bacteria remain for an extended time for the same reason and cause an ongoing immune response. Researchers continuing to work to find better ways to determine when the immune response is due to ongoing infection and when it is due to these post-infection factors.

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Treatment

Treatment of infections in immune privileged sites is complicated because doctors face the same challenges that the body does itself: the need to both protect the tissue from damage and also cure the infection. Protection is generally offered by reducing the immune response through the use of steroids. However, this can allow the pathogen even greater refuge. It may even allow the pathogen to escape the site and infect other areas of the body.

Consequently, antiviral or antibiotic medications are added, but treating physicians in case studies regularly comment that they wish they had more information about the best courses of treatment for these cases. With tick-borne infections, treatment can become even more complex as information is needed about various combinations of co-infections.

Even before treatment is initiated, effective testing is needed. Pathogens that are in a refuge area may not generate a detectable response from the host immune system and may be hard to find using direct detection laboratory techniques. Galaxy Diagnostics has pioneered advances in the detection of tick-borne bacteria so that providers can start with more accurate laboratory support of their diagnosis.