I am doing a comparative study of two different viruses. When I infected mice with the wild-type viruses, the mice will show weight loss but eventually recover. But in case of the mutant virus infection, the mice will eventually die. The mutant virus is, in a way, more virulent than the wild-type virus.
When assessed for the different cell type recruitment in the lungs (infection was done intranasally), we find that wild-type virus-infected lungs had higher NK cells compared to the mutant virus-infected lungs, whereas, in the mutant virus-infected lungs we see higher neutrophil accumulation.
But, I am finding it difficult to connect the recruitment of neutrophils to the fatal consequence of the mutant virus-infected mice. What am I missing?
The mutant virus may
1) Evade cytotoxic NK Cells and recruit effector NK cells. I propose checking CD56brightCD16- NK cell population in mutant virus infection.
2) This recruitment may induce high release of cytokines and chemokines that would eventually attract neutrophils to the site. Higher amount of neutrophil recruitment lead to systemic inflammation and NETosis. 10.1189/jlb.4VMR1114-555R This review can show you what you need to know about neutrophil recruitment in viral infections.
Hello,
maybe you look at neutrophil-mediated immunopathology instead of direct cytopathic effects caused by your strains.
Give it a read here:
Article The host immune response in respiratory virus infection: bal...
https://www.nature.com/articles/nri2802
Özgür Albayrak thank you for this suggestion, I would try to look at the Cd56brightCD16dim NK cell population. But I have a concern, even though the neutrophil recruited in the lungs of mutant virus-infected mice show consistently higher than that recruited in the wild-type virus-infected mice, the percentage is ~20% of the CD45.2-hematopoietic cells. Is that really enough to bring about a detrimental effect on the tissue as well as the animal as a whole?
Sebastian Weis while I have considered looking into the immunopathological effects of high neutrophil recruitment in the lungs, it seems a bit dicey to me that ~20% of the immune cells in the lungs being neutrophil by the 6th day post-infection, is enough to kill the host. In fact, I am also considering the effects of non-immune cells, the mesenchymal cells, in response to the infection. I had tried a small experiment where I looked at the matrix metalloprotease activity through gelatin zymography, and found that the MMP-9 activity was higher in the WILD-TYPE virus-infected lungs compared to the mutant virus-infected lungs. This leads me to think that there is something related to the inability of the mutant virus-infected mice to repair their tissues. What are your thoughts?
We had something like this in a study where post infection in 4th day had elevated neutrophil count and the animals died due to this and there was no bacterial contamination in the area however 50% of the cells were neutrophils.
Hello Suktika,
which again would go into the direction of immunopathology, right. Impaired tissue damage control does not argue agains immunopathology (Article Tissue damage control in disease tolerance
). Also, I am not aware of any thresholds of neutrophil counts that determine the faith of the host. Maybe there is literature. See also here for MMP9a and Neutrophils:Article Complex regulation of neutrophil-derived MMP-9 secretion in ...
It is a different model then yours, but the work might contain some interesting informations. However, you are right in can go both ways, if the virus is more cytopathic, this could cause increased Neutrophil/Monocyte influx. Any data for this? What about cytokines, BAL cell contents, barrier dysfunction, pathogen loads etc. is this all consistent with an altered immune response or do you only see the NK/Neutrophil ration changed?