Investigating the Effects of Traffic-Generated Air-Pollution on the Microbiome and Immune Responses in Lungs of Wildtype Mice Page: 87
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causing degradation of IgA in the groups exposed to high -fat (HF; 21% fat by content), resulting
in reduced immune surveillance against the bacterial commensals present within the lungs. The
diminished immune response may have resulted in the bacterial outgrowth of Proteobacteria within
the lungs. Apart from the degradation of IgA observed with ME and HF exposures, we suspect the
oxidative stress responses may increase nitrate availability providing selective nutrients for the
outgrowth of Proteobacteria. Proteobacteria bloom has been documented to occur in inflammatory
environments with excess ROS+RNS products (nitrates) (Scales et al., 2016). Our IgA results
show that there is a significant interaction between HF diet and ME exposures suggesting that
consumption of the HF diet is causing further harm to the host. High-fat diet consumption has been
shown to induce higher levels of neutrophil recruitment, and the effects in combination with ME
exposures may be causing an unregulated increase in neutrophil elastase leading to the degradation
of IgA (Moorthy et al., 2016). Neutrophils are likely the primary cells responsible for both IgA
degradation and oxidative stress responses, which could facilitate the outgrowth of pathogenic
bacteria belonging to the Proteobacteria phylum. Although we were unable to test our hypothesis
with the ME study, we were able to determine the presence of peroxynitrite and its involvement in
the bacterial dysbiosis observed with the DEP exposure study.
In our DEP study, we observed an increase in peroxynitrite and detected increased
expression of nuclear transcriptional factors and inflammatory gene expression. Oxidative stress
has also been shown to induce the NF-KB mediated gene transcription (Kabe et al., 2005). The
upregulation in NF-xB observed with DEP exposures may be either due to oxidative stress
responses or due to the activation by Toll-like receptors (TLR) - 2 and 4. TLRs are activated in
response to bacterial ligands such as gram-negative bacterial cell wall components - LPS and
peptidoglycans from gram-positive bacteria. We suspect that the endotoxins present on the DEP87
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Daniel, Sarah. Investigating the Effects of Traffic-Generated Air-Pollution on the Microbiome and Immune Responses in Lungs of Wildtype Mice, dissertation, December 2020; Denton, Texas. (https://digital.library.unt.edu/ark:/67531/metadc1752346/m1/99/?q=j+w+gardner: accessed June 27, 2024), University of North Texas Libraries, UNT Digital Library, https://digital.library.unt.edu; .