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Monday, November 4, 2013

Pathogen Mode of Entry Has a Significant Effect On Host Adaptation


In order for us to properly understand the diseases that make us sick we must examine the entire mechanism the pathogen (disease causing agent) uses to invade our bodies. Much experimental work has been done to understand the pathogen mechanism once it has generated an immune response in the body, however one of the most important steps in the mechanism, which hasn’t really been experimentally studied, is the mode of entry. There are two major ways that a pathogen can enter the body, either through ingestion (orally) or systematically (a prick or needle). When a pathogen enters the body systematically it bypasses much of the innate physiological and anatomical barriers that prevent pathogen entry, like our skin, sweat, oils and mucus we secrete. In contrast, a pathogen must overcome many more barriers when entering the body orally, for instance saliva.

It has been shown in a recent experiment that the path of pathogen entry affects the rate at which the pathogen is eliminated and the way that it responds to the same type of pathogen. In the experiment equal amounts of both male and female Drosophila melanogaster flies were administered with one of two treatments of P. entomophila bacterial strain. Half the male and female flies were introduced to P. entomophila orally (BactOral), whereby food plates were coated in the bacterial strain. The other half of male and female flies was injected in the thoracic (area where the legs and wings attach) region with P. entomophilia (BactSys). Controls for both the injection (ContSys) and food treatments (ContOral) were also observed in the experiment. The mortality of the flies was measured for at least 10 days. It was found that the survival rate of the flies was much higher when the bacterial strain was introduced orally. The evolution of resistance to the particular bacterial strain also developed much faster when P. entomophilia was introduced orally.

These results reaffirm the theoretical notion that oral pathogens have to overcome more physical barriers in order for them to enter the body cavity. This is in contrast to a systematic infection because the physical barriers, like the skin have already been bypassed and the bacteria have been directly injected into the body cavity. So when a pathogen enters systematically the body must rely on other, more active ways of identifying and eliminating the invader, namely through members of the immune system that belong to the adaptive (more-specific) response like plasmatocytes. These more complex and specific ways of eliminating the invader are slower to act because B cells must be activated to produce antibodies, that than must find the pathogen and kill it, whereas much of the pathogen that was introduced to the mice orally didn’t really require the activation of the adaptive immune response. It only had to rely on the innate (more general) immune response and physiologic barriers that were already in place like the mucosa layers of the respiratory and gastrointestinal tracts to prevent pathogen entry into the body cavity. Since these defenses are already localized to the site of pathogen entry and need no further activation, the immune response is much faster when the pathogen is administered orally rather than systematically.








The results in this experiment illustrated the importance of the route of pathogen entry. It was found that pathogen entry affected survival rates in flies but we can extrapolate this to a greater context. The fact that the rate of the immune response depended on the way in which the pathogen entered the flies demonstrates that the mode of entry makes a huge difference on how great of an impact the pathogen causes on the host. This is vital for the study of human immunology because if the mode of entry impacts the ability of our body to fight off an invader than we need to understand the reasoning behind it, so we are better able to prevent disease and the impact of pathogen infection. It was found that the Drosophila melanogaster flies that were able to resist bacteria through oral consumption were unable to resist the same bacteria infection through systematic entry and vice versa. This also alerts immunologists to the fact that for humans, elimination of a pathogen that is ingested orally will not guarantee the person will be protected from the same pathogen if it enters systematically. It stresses the importance of complete knowledge of the different mechanisms the immune system takes to eliminate an oral pathogen versus a systematic pathogen.

One of the most important things about this research article was that it provided actual experimental evidence to back up the theory that mode of pathogen entry impacted host adaptation. It alerted researchers to the importance of studying the full mechanism of pathogen infection, especially the mode of entry and it reinforces the necessity that the mechanism of pathogen entry be included when categorizing and studying host-pathogen interactions. 

This article emphasized the importance of doing future experiments and gaining experimental evidence to figure out the effect that transmission mode plays on the host-pathogen interactions. Previous studies on the evolution of virulence (harmfulness) patterns in natural populations may be at odds with the conclusions found in this experiment, so it is important to gain experimental evidence (other than observation) to see what the actual underlying cause of the patterns observed is. Once we gain insight into the actual impact that the mode of pathogen entry causes we can begin to use this information to better protect us against more harmful infections that are harder for our immune system to combat. We also will better be able to classify various pathogens and develop more affective vaccines that could help improve overall human immunity to pathogens.

Primary Source:
Martins NE, Faria VG, Teixeira L, Magalhães S, Sucena É (2013) Host Adaptation Is Contingent upon the Infection Route Taken by Pathogens. PLoS Pathog 9(9): e1003601. <http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003601>

Images:

Other Sources:
2. http://link.springer.com/article/10.1007/BF02692179#page-1

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