FROM ANIMALS TO HUMANS: THE DEADLIEST CATCH

Original Article: Maggio, S., Takeda k., Stark, F., Meirovics,A. I., Yabe, I., & Cowley , S.C. (2015). Control of Francisella tularensis Intracellular Growth by Pulmonary Epithelial Cells Post By: Jana Woods

Francisella tularensis is an intracellular bacterium that can be transmitted from animal to humans. This facilitative intracellular bacterium, typically exist primarily in animals but can have the possibility of infecting humans.  F. tularensis is a rod – shaped coccobacillus and a species of gram negative bacterium. F. tularensis is the causative agent of tularemia. Tularemia causes a deadly   feverish illness. F. tularensis can enter and infects its host through different methods.  Some of these methods include gastrointestinal tracts, respiratory tracts, and broken skin.  The most virulent form of the disease is respiratory tularemia. F.tularensis can essentially infect most types of cell. However, this facilitative intracellular bacterium is known for primarily infecting microphages (a type of large white blood cells) within the host organism. 

Phagocytosis allows F. tularensis to enter into the microphage.

F. tularensis (blue) infecting host

Phagocytosis is the ingestion of bacteria by phagocytes.  Now that the microphage has ingested its deadliest catch how will the immune system be able to deal with this lethal organism? In 2015 a study was conducted to test the possibility that cytokines can activate epithelial cells to create anti- microbial factors that would in turn put a constraint Francisella growth. The researchers in this studied used a combination of cytokines that would be used to activate murine pulmonary epithelial cells, and would consequently inhibit the intracellular growth of the  LVS (live vaccine strain) and the lethal F. tularensis Schu S4 strain. The combination of the particular cytokines used were interferon-gamma( IFN-γ) that are used to activate microphages, tumor necrosis factor (TNF) which help to produce reactive nitrogen intermediates, and IL-I7A. A gene expression analysis was completed and showed that NOS₂ is up-regulated in infected cytokine treated cells of F. tularensis. When NOS2 is in the microphage it kills the bacterium that has been engulfed within it. The treatment of live virus strains infected the pulmonary epithelial cells with an iNOS₂inhibitor overturned live virus strain killing. Through this, researchers then found that iNOS2 was an antimicrobial mechanism that helped to inhibit intracellular growth of bacteria. 

 



Figure 1-A and 1-B illustrates how pulmonary epithelial cells are resistant to antimicrobial effects with cytokine treatment (as shown in 1-B) in comparison to those epithelial cells in 1-A. RNI-independent mechanisms were looked at because the researchers believed that they may limit F. tularensis intracellular growth. When conducting research on Cytokine-induced control of F. tularensis LVS growth in pulmonary epithelial cells, the researcher’s results that suggested that TC-1 cells displayed the highest LVS invasion occurrence. TC-1 cells help to define the intracellular trafficking of LVS during infection of pulmonary epithelial cells. Pulmonary epithelial cells exploited RNI to control LVS intracellular growth. A substantial quantity of cytokine-induced LVS growth inhibition was RNI-independent. The results also suggest that pulmonary epithelial cells require a combination of IFN-γ and TNF in order to exercise maximal control of F. tularensis intracellular growth. Not only can Francisella grow in microphages, but it has been recently discovered that it can flourish in a variety of host cells vivo (in the organism) and invivo (outside the organism). The capability of these cells to express iNOS both in vitro and during invivo respiratory LVS infection showed that these pulmonary epithelial cells dynamically contribute to the control of Francisella infection through the production of antimicrobial products .Little evidence is known in regards to the killing of F. tularensis when it is not in the microphage cell type. Murine pulmonary epithelial cells have the ability to inhibit F. tularensis’s intracellular growth when coupled with specific combinations of epithelial cells. When F. tularensis is released into the cytosol it quickly multiplies. Being that this organism multiples so quickly it makes it difficult for the immune system to sequester. In furthering this research, researchers have been looking into the effects of F. t. mediasiatica (a species that is very similar to F. tularensis ) when coupled with the same combination of cytokines, in order to observe if F. tularensis’s intracellular growth is also inhibited. When looking at the effects researchers are determining how it can also affect humans. Moreover, by observing the results researchers are then trying to determine if this subspecies is virulent or not. 

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Figure 1-A and 1-B illustrates how pulmonary epithelial cells are resistant to antimicrobial effects with cytokine treatment (as shown in 1-B) in comparison to those epithelial cells in 1-A. RNI-independent mechanisms were looked at because the researchers believed that they may limit F. tularensis intracellular growth. When conducting research on Cytokine-induced control of F. tularensis LVS growth in pulmonary epithelial cells, the researcher’s results that suggested that TC-1 cells displayed the highest LVS invasion occurrence. TC-1 cells help to define the intracellular trafficking of LVS during infection of pulmonary epithelial cells. Pulmonary epithelial cells exploited RNI to control LVS intracellular growth. A substantial quantity of cytokine-induced LVS growth inhibition was RNI-independent. The results also suggest that pulmonary epithelial cells require a combination of IFN-γ and TNF in order to exercise maximal control of F. tularensis intracellular growth. Not only can Francisella grow in microphages, but it has been recently discovered that it can flourish in a variety of host cells vivo (in the organism) and invivo (outside the organism). The capability of these cells to express iNOS both in vitro and during invivo respiratory LVS infection showed that these pulmonary epithelial cells dynamically contribute to the control of Francisella infection through the production of antimicrobial products .Little evidence is known in regards to the killing of F. tularensis when it is not in the microphage cell type. Murine pulmonary epithelial cells have the ability to inhibit F. tularensis’s intracellular growth when coupled with specific combinations of epithelial cells. When F. tularensis is released into the cytosol it quickly multiplies. Being that this organism multiples so quickly it makes it difficult for the immune system to sequester. In furthering this research, researchers have been looking into the effects of F. t. mediasiatica (a species that is very similar to F. tularensis ) when coupled with the same combination of cytokines, in order to observe if F. tularensis’s intracellular growth is also inhibited. When looking at the effects researchers are determining how it can also affect humans. Moreover, by observing the results researchers are then trying to determine if this subspecies is virulent or not. 

 

Citations

Maggio, S., Takeda k., Stark, F., Meirovics,A. I., Yabe, I., & Cowley , S.C. (2015). Control of Francisella tularensis Intracellular Growth by Pulmonary Epithelial Cells