Hostname: page-component-77c89778f8-7drxs Total loading time: 0 Render date: 2024-07-19T02:07:56.112Z Has data issue: false hasContentIssue false

458 Influence of a Gastrointestinal Infection on Lung Immunity

Published online by Cambridge University Press:  03 April 2024

Karlin Blackwell
Affiliation:
Montana State University
Heather Walk
Affiliation:
Montana State University
Douglas Kominsky
Affiliation:
Montana State University
Seth Walk
Affiliation:
Montana State University
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

OBJECTIVES/GOALS: We aim to characterize how Heligmosomoides polygyrus bakeri (H. poly) alleviates murine allergic asthma which shares many characteristics of human asthma. This approach of has already identified helminth-produced human immune cell ligand “mimics” that hold great potential for next-generation clinical biologics METHODS/STUDY POPULATION: We examined the lung tissue of C57BL/6 mice infected with H. poly for changes in the pulmonary microenvironment. At ten days post infection, four infected mice and two co-housed uninfected mice were sacrificed, and their lung tissue harvested for examination of RNA via RT-qPCR. This design allows for the comparison between the lung microenvironments of infected and naīve mice. In future experiments, we intend to characterize what small molecules produced by the helminth drive changes in the lung using germ-free models of H. poly infection. RESULTS/ANTICIPATED RESULTS: We found key differences in lung chemokines between mice infected with H. poly and naīve mice. Using a student t-test with naīve correction for variance, we were able to show significant differences in the expression of E cadherin (p = 0.0355), CXCL10 (p = 0.0025), CX3CL1 (p = 0.0029), CCR2 (p = 0.017), and IDO1 (0.0078). We also found that differences in the expression of CCL5 bordered on significant with a p-value of 0.066. The expression of most of these markers (CXCL10, CCR2, CCL5, and IDO1) was elevated in the lungs of infected mice compared to naīve controls. In contrast, E cadherin and CX3CL1 showed the opposite trend with naīve mice showing greater expression. These clear differences in lung tissue gene expression underscore the connection between the gastrointestinal and pulmonary mucosal immune compartments. DISCUSSION/SIGNIFICANCE: The changes are unexpected for an infection that has been shown to attenuate allergic inflammation in the lung with increases in the IFN-Y responsive genes IDO1 and CXCL10 and inflammatory lung markers, CCL5 and CCR2. In contrast, there were decreases in inflammatory lung marker CX3CL1 and the tight junction protein E cadherin in infected mice.

Type
Precision Medicine/Health
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NCCreative Common License - ND
This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.
Copyright
© The Author(s), 2024. The Association for Clinical and Translational Science