Abstract
Abstract
Background
MiR-146a, an effector mediator, targets Notch-1 and regulates the innate and adaptive immune systems response. Recently, we reported that Notch-1 signaling plays a key role in macrophage polarization and response during infection. We employed Mycobacterium avium paratuberculosis (MAP) infection in Crohn’s disease (CD) as a model to demonstrate the role of Notch-1/IL-6 signaling on MCL-1 based apoptosis and intracellular MAP infection and persistence. This study was designed to investigate the impact of polymorphisms in miR146a on the immune response and infection in our MAP-CD model.
Methods
We determined the incidence of miR-146a rs2910164 G > C in 42 blood samples from clinical CD patients and controls. We also measured the effect of rs2910164 on expression of Notch-1 and IL-6, and plasma IL-6 protein levels in our study group. Finally, we analyzed the blood samples for MAP DNA and studied any correlation with miR-146a polymorphism. Samples were analyzed for statistical significance using unpaired tow-tailed t-test, unpaired two-tailed z-score and odds ratio. P < 0.05 considered significant.
Results
MiR-146a rs2910164 GC was detected at a higher incidence in CD (52.6%) compared to healthy controls (21.7%) rs2910164 GC Heterozygous polymorphism upregulated Notch-1 and IL-6, by 0.9 and 1.7-fold, respectively. As expected, MAP infection was detected more in CD samples (63%) compared to healthy controls (9%). Surprisingly, MAP infection was detected at a higher rate in samples with rs2910164 GC (67%) compared to samples with normal genotype (33%).
Conclusions
The data clearly associates miR-146a rs2910164 GC with an overactive immune response and increases the risk to acquire infection. The study is even more relevant now in our efforts to understand susceptibility to SARS-CoV-2 infection and the development of COVID-19. This study suggests that genetic variations among COVID-19 patients may predict who is at a higher risk of acquiring infection, developing exacerbating symptoms, and possibly death. A high scale study with more clinical samples from different disease groups is planned.
Funder
This work was funded, in part, by the Florida Legislative Grant.
Publisher
Springer Science and Business Media LLC
Subject
Infectious Diseases,Virology,Gastroenterology,Microbiology,Parasitology
Cited by
11 articles.
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