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