18 Responses

  1. Zachary Davis
    Zachary Davis at | | Reply

    It is interesting to me that bats possess a less debilitating inflammation response due to their unique method of transcriptional priming of the NLRP3 protein genes; this is mostly because they serve as common reservoirs of diseases such as rabies and Ebola. Particularly interesting is the ascertainment of the fact that bats are typically able to handle a greater viral load as a result of this reduced immune response; it is not necessarily that they can fight the infection better than humans or mice, but that their ability to dampen immune responses prevents them from dying due to their own bodies’ actions. This is important in the spread of disease itself; while bats may show no outward symptoms due to this adaptation, they can easily spread infections to organisms with less robust or less advanced inflammation responses; in particular, livestock, such as cattle and pigs, and humans possess inflammasomes that possess the PHYIN family AIM2 inflammasome gene. This gene is primarily responsible for activation of inflammation responses in most mammals, and is absent in bats, which is likely related to the down-regulation of NLRP3 transcription. Suppression of this gene in humans or livestock could, in theory, allow for better treatment of infectious diseases (preventing haywire inflammatory responses from killing the host before treatment can be effective) and non-infectious diseases that involve chronic inflammation (such as type 2 diabetes mellitus or various autoimmune disorders).


    1. Kandace Barzey
      Kandace Barzey at | | Reply

      I find it interesting that even though majority of mammals possess the PYHIN family AIM2 inflammasome gene, that bats don’t possess this gene; this explains why the humans and livestock show activation of an inflammatory response, while it is absent in bats. While this trait is beneficial in the case of an uncontrolled inflammatory response, there are also implications that come along. A case study involving two bat species (Pteropus Alecto and Myotis davidii) reveals the absence of the PYHIN gene family. I chose this article because it speaks of the loss of the PYHIN gene family in bats and the implications for inflammasome sensing. Divergence of the PYHIN gene between bat lineages causes a loss of function histories in reference to bat evolution; while other mammals will have at least one gene member, bats have lost their entire family. In addition to that, the loss of this gene leads to the removal of inflammasome DNA sensors. The removal of these sensors indicates an important adaptation that is flight induced and related to pathogen-host co-existence.


  2. Donzell Jones
    Donzell Jones at | | Reply

    After reading this blog post, I realized that the inflammatory response is important in humans in order to help fight infections, however, when this response is poorly controlled, it can result to damage in the body caused by diseases. Bats are known to host many fatal viruses without suffering from diseases that humans would experience if infected by these viruses. This is due to the reduction of the inflammation mediated protein, NLRP3, which is found to trigger the body’s response to fight off infection through induced inflammation. Since NLRP3 is responsible for the survival of bats by limiting excessive virus-induced inflammation, I concluded that using specific drugs to inhibit the activation of NLRP3 will help prevent the over excessive inflammatory response that causes damage to tissues and organs in the body. In a recent article, they discussed the targeting of the NLRP3 inflammasome in inflammatory diseases. This article explains how the activation of NLRP3 leads to the activation of the interleukin-1β cytokines, which induces an inflammatory response, resulting in pyroptotic cell death (Mangan, 2018). I chose this article because it supports my idea of using the potential of NLRP3 as a drug target by pharmacological inhibition. Further understanding of the structure and activation mechanisms of NLRP3 is needed in order to create opportunities for pharmacologically targeting NLRP3.


    1. Amber Louis
      Amber Louis at | | Reply

      I find your post very interesting and completely agree with your idea. Based on this article that I found, it shows that activation of the NLRP3 inflammasome is related to chronic inflammatory disease. However, it states that it occurs due to danger molecules signaling the activation of NLRP3. Their research showed that the endogenous danger signaling molecules produced oxidized phosphatidylcholines which induced the inflammasome. Since these oxidized lipids play a role in NLRP3 activation, should scientists be looking further into creating something that targets those lipids to reduce possibility of getting chronic inflammatory disease?


    2. Katherine Stennett
      Katherine Stennett at | | Reply

      Upon reading your response regarding the article you suggested to support your idea, I found that I agreed with this conclusion. In theory it seems like a great approach on this issue in humans. My concern is in suppressing the NLRP3, how might the body respond when inflammation is truly needed. It is there to activate in response to certain stressors in the body. If we don’t know how much of NLRP3 is needed to alert the body that something is indeed wrong, suppressing it may prevent the response when it is truly needed. After reading the article I agree that more needs to be known about the structure and activation mechanisms of NLRP3. I would be curious to know how they might regulate how different stimuli effect the signaling. This seems that in humans and other larger mammals, it is something that is needed to a degree. Suppressing it completely could prove detrimental. I would defiantly consider why it is not needed in bats in comparison to other mammals.

  3. Aasiya Mujeeb
    Aasiya Mujeeb at | | Reply

    I think it’s fascinating how bats can carry so many diseases, yet not become susceptible to them due to their higher tolerance. They act as transport vessels of diseases that infect humans while managing to not falling ill themselves. The source I chose includes reasons and methods as to how bats can achieve this, which I found to be a useful supplement to the discussion post. The paper explores the possibility of bats having greater combinations of immunoglobulin genes that do not experience maturation to be one of the causes as to why bats are tolerant to the diseases they carry. The paper also mentions that bat viruses have evolved in interferon rich environments, which allowed them to develop specific measures against the interferon response. In humans, the interferon response is not as developed, making us more susceptible to these diseases. I think this is an interesting area of research to further help develop ways to make the human immune response stronger.


  4. Kandace Barzey
    Kandace Barzey at | | Reply

    I found this article interesting for the simple fact that we learn how an inflammatory response is beneficial in helping humans fight infections, when properly controlled. However, when the inflammatory response is uncontrolled, it can lead to damage that was caused by the disease. It is expected that this would be the case among all mammals, but bats have the ability to limit inflammation, causing a less amount of damage to the body. A bat’s ability to limit inflammation is mediated the NLRP3 protein which normally triggers the body’s response to fight off infection; this protein is very reduced in bats. In a recent article, a NLRP3 inflammasome inhibitor, by the name of JC124, has been shown to alleviate the neuroinflammatory response that follows after a traumatic brain injury. Results showed that post-injury treatment with JC124 lead to a significant decrease in the number of injury induced degenerating neurons and a decreased inflammatory cell response in the brain. Using a NLRP3 inflammasome inhibitor such as JC124 is very beneficial when dealing with an uncontrolled inflammatory cell response in the brain. Taking this same concept and developing different inflammasome inhibitors for different parts of the human body would potentially lead to better treatment of these infectious diseases along with a major decrease in the damage caused by them in the human body.


  5. Kedan Endrias
    Kedan Endrias at | | Reply

    This article highlights the role that the protein NLRP3 plays within the immune system in bats and humans. As an inflammation detector, when the body is under high levels of stress, it works to activate a variety of mechanisms to strengthen immune response. However in bats, they have a less active form of the protein, yet are still able to be immune from viruses including Ebola, SARS and MERS. I began to wonder how inactive forms could be more beneficial that active forms of NLRP3. I found an article that studied how NLRP3 works in neutrophil IL-1β secretion during streptococcus pneumonia infection. The study found that in mice infected with S. pneumoniae NLRP3 is involved in neutrophil IL-1β secretion, though more research needs to be done to determine the direct mechanism. I think both articles are important and more research should be done to determine the mechanism of how NLRP3 works, so that possible vaccines could be developed in the future to help humans become immune from these viruses.


    1. Kenton G
      Kenton G at | | Reply

      After reading your article, I was interested to see what other effects the NLRP3 inflammasome has on the immune system. It seems that the NLRP3 inflammasome has multiple ways of helping the body fight against cancerous cells. Aside from the secretions of IL-2ß which primes CD8+ T cells, the inflammasome can also produce IL-18. The cytokine IL-18 is responsible for recruiting the help of natural killer cells. These cells play a major role in limiting the metastatic activity of colon carcinomas within the liver. The study showed that mice with defective inflammasomes had increased tumor growth. Since NLRP3 has such a wide range of defense mechanisms, it would be interesting to see which cancers are associated with a defective NLRP3 gene and if there have been specific treatments created for them.


  6. Susmita Dey
    Susmita Dey at | | Reply

    We often state bat as a scenario of viruses’ carrier or causing harmful parasitic infection to humans. Even though we know, the most common viruses they carry are SARS, MERS, and few others. Well, it is quite interesting to learn from this article that if the human can get infected from such infectious diseases by interacting with bats or from the bite of bats. Then, how these bats can keep them healthy and their immune system is not reacting to such pathogen they are carrying? The scientific study showed that they are resistant to such inflammation of those infections which is due to NLRP3 protein suppressing their inflammatory responses leading to their immune cells damage free. However; the researchers studied two models of mice and humans to compare the responses of the immune cells with bats which showed that upregulation of inflammation-mediated NLRP3 protein was much reduced in bats than mice and humans. It is found that the genetic transcriptional factor is playing the key role in limiting the stimulation of NLRP3 protein in bats oppositely which is triggered for activation in mammals leading to cell death. Since the NLRP3 gene is enabling the survival rate of bats in specific species but they can infect humans leading to severe pathogenic diseases. I choose this article to support that human infection needs to be controlled by elucidating the molecular mechanism of NLPR3 activation. It can be done by introducing narrow-spectrum drug or antipathogenic drug which specifically reduces the production of the pro-inflammatory signals thus able to downregulate the NLPR3 stimulation. I found in a recent article, that cytosolic calcium fluxes are involved in NLRP3 activation in response to the pathogen in human bodies. Thus, physiologically inhibiting the NLPR3 protein by specific drug will reduce the secretion of the interleukin and prevent tissue damages in humans causing major diseases from such infection.


  7. Sherrose Nazim
    Sherrose Nazim at | | Reply

    I found this blog post to be fascinating and surprising; I had no idea that bats can carry so many deadly viral infections inside them and not be harmed by them. Bats are associated with vampires, mystical creatures, and horror stories in the western countries, so to find out that in China they are viewed as a symbol of happiness or good-luck, it may be shocking to many Americans. After reading this blog post, I found it very interesting that because of limited inflammation, bats can tolerate the infection and survive. In humans and mice, a poorly controlled inflammatory response might damage the body because of the infectious disease. I also found it interesting that from the research conducted; researchers found that in bats the protein responsible for inflammation (NLRP3) was significantly reduced. This information brought me to realize that limited inflammation could be very beneficial to humans rather than a poorly controlled inflammation response.
    Furthermore, Since bats can tolerate viral infections, does this mean that they are resistant to diseases? The answer is no; bats are susceptible to many other infectious diseases such as white-nose syndrome. White-nose syndrome is a fungal infection that has killed millions of bats in North America. I have attached the article below that shows many challenges and opportunities that bat’s immune systems encounter.


    1. Irene Avalos
      Irene Avalos at | | Reply

      I also thought about the lore surrounding bats and how it differs between different countries! I recently saw an article call them ‘flying puppies,’ and it’s stuck with me since. It was fascinating to learn about bats being reservoirs for various viral diseases. Reading your article prompted me to look into how their virulence compares to other organisms. This article I found compares their virulence to another common reservoir for diseases, rodents. They found that bats can host more zoonotic viruses and in larger volumes when compared to rodents. However, they mentioned that since there are much more rodent species than bat species, the overall number of zoonic viruses was higher in the rodents. I still question though, if bats can host multiple serious diseases per species, shouldn’t we worry about those more? Like they say, ‘quality over quantity.’


  8. Afuah
    Afuah at | | Reply

    One question I’ve always wondered is why certain animals can pass particular viral or bacterial strains to humans, and those strains cause more severe effects in humans. This article highlighted the importance of immunological differences among species such as bats and humans. Even though we may have joint inflammation mediated proteins such as NLRP3, slight variations in their structure due to evolution causes them to work differently. To better understand inflammation pathways in general, I sought out to understand the mechanism of the NLRP3 pathways. While it was difficult to find further studies of bats in regards to viral load and NLRP3-mediated inflammation, I did see a study on how this pathway is used observed in osteoarthritis which occurs when cartilage deteriorates. In hand osteoarthritis, HOA, it is found that interleukin IL-1β is an inactive precursor protein that needs an inflammasome for its activation. The purpose of this study is to understand how IL-1β and NLRP3 inflammasome correlate to one another in humans with HOA. It was found that there was an overexpression of NLRP3 protein in patients with non-erosive HOA compared to healthy individuals. Similar to this article was stating that reduced inflammation is caused by different variants of the NLRP3 protein in mammals, in HOA it depends on various options of interleukins expressed. When the expression of IL-6 and 7 was undetectable, expression of IL-1β was positively correlated to joint swelling.


  9. Amber Louis
    Amber Louis at | | Reply

    Reading this article I was able to finally grasp a reason as to why bats are able to avoid sickness, after being a reservoir for many diseases. I found this article interesting because it brings up many questions to see if there are ways to control the inflammatory response in humans. Bats are able to have a controlled inflammatory response due to their ability to down regulate a transcriptional priming which aids in upregulation of the NLRP3 protein. Since this protein is not being expressed as much, their inflammatory response is more controlled and doesn’t really respond to a lot of stress the immune system would cause. While it is interesting that the inflammatory response is reduced in bats, it made me wonder if the viruses that invade bats are really effective towards them; maybe the bats are just being used as reservoirs. I was able to find an article that shows Hepatitis C virus (HCV) is responsible for inducing the NLRP3 inflammasome and IL-1β from hepatic macrophages in humans. This in turn will induce a hepatic inflammatory response. HCV is able to do this through a core protein that acts as an inflammasome activator (Negash, et. Al). If viruses are causing the upregulation of NLRP3 protein, is it possible to look at targeting the core protein in the virus to inhibit our inflammasome activation?


  10. Sabrina Bernard
    Sabrina Bernard at | | Reply

    Inflammation is supposed to be a good thing- a way the immune system is alerted”. However, is it doing more harm than good? The article was interesting because it looked into bats and their decrease of NLRP3. Therefore, without this protein there is less inflammation. Should humans find a way to decrease inflammation..I found an article discussing how much damage non-infectious agents can do to the inflammatory pathways. Severe diseases are formed because an over activation of the immune system such as cancer, and lupus. Inflammation is frequently a key element in the pathological progression of organ disease. Three main pathways that leads to inflammation are NF-κB, MAPK, and JAK-STAT. This article highlight each major organs and the specific mechanism that lead to inflammation..I believe we should focus on a more detailed way to incorporated an “under attack” for certain diseases.


    1. Sherrose Nazim
      Sherrose Nazim at | | Reply

      After reading your comment and article, I also began to think about how much damage non-infectious agents can do to the inflammatory pathway. You have stated in your comment that “there are three main pathways which lead to inflammation which are NF-kB, MAPK, and JAK-STAT”. After doing some research, I have found that Interleukin-32 which is a cytokine is also involved in inflammation and cancer development. IL-32 is expressed by activated Natural killer cells and activated T-cells. IL-32 is induced by pathogens and pro-inflammatory cytokines. The article linked below talks about several reports showing IL-32 is upregulated in patients with several inflammatory diseases and is induced by inflammatory responses. Furthermore, the article suggests that IL-32 could be the target of many diseases and the therapeutic agents for targeting IL-32 which could benefit the treatment of cancers and inflammatory diseases.


  11. Mengzhu Tang
    Mengzhu Tang at | | Reply

    The most surprising fact that I found in this post is that bats can carry so many viruses without suffering from the diseases that these pathogens cause in humans. The reason provided by the original post is that inflammation mediated by inflammation sensor NLRP3 was significantly reduced in bats. That is something similar in last post “An Innate Immune Sensor Suppresses Liver Cancer” that I read, and I was thinking if we could inhibit the activation of NLRP3 inflammasome, some human infectious diseases would be controlled.
    The article I chose below explains that signaling pathways controlling NLRP3 inflammasome assembly, regulation of the NLRP3 inflammasome has been most extensively investigated in macrophages. In these cells, NLRP3 inflammasome assembly results from a two-step process referred to as priming and activation. The priming signal usually corresponds to cytokines or DAMPs/ PAMPs recognized by receptors that transcriptionally control the expression of numerous genes. The activation signal can be provided by various cellular stresses and is transcription independent. Accordingly, NLRP3 inflammasome assembly is strictly regulated by the requirement of coordinated priming and activation signals. And inhibiting the priming and activation signals could be one way to control NLRP3 inflammasome and limit inflammatory in the human body.


  12. staicy odhiambo
    staicy odhiambo at | | Reply

    This topic is particularly interesting because it talks about a topic we went into detail over class. We have learned that the inflammatory response is a form of positive feedback loop that is activated when we have invaders in our body. We also checked into how too great of an inflammatory response is responsible for the disease state of most infections. I think this mechanism that bats have formed can be very beneficial in studying to increase our knowledge of immunity and medicine to treat most pathogenic infections. We see that bats are able to gain immunity to the pathogens they serve as a reservoir to by limiting their inflammatory response. This is done by transcriptional priming of NLRP3, an inflammatory sensor, and reducing this gene in bats. A research comparing pro- and anti- inflammatory response in paired human primary airway has revealed that regulating immune negative effects can prevent excessive lung inflammation during respiratory infection. It is well known that over inflammation leads to tissue damage, so decreasing inflammation has some promising effects on less damage.


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