Title | Bacterial expression of a designed single-chain IL-10 prevents severe lung inflammation. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Montero-Blay A, Blanco JDelgado, Rodriguez-Arce I, Lastrucci C, Piñero-Lambea C, Lluch-Senar M, Serrano L |
Journal | Mol Syst Biol |
Volume | 19 |
Issue | 1 |
Pagination | e11037 |
Date Published | 2023 Jan |
ISSN | 1744-4292 |
Keywords | Animals, Bacteria, Cytokines, Humans, Inflammation, Interleukin-10, Lung, Mice, Pneumonia, Pseudomonas aeruginosa |
Abstract | Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is active as a swapped domain dimer and is used in bacterial therapy of gut inflammation. IL-10 can be used as treatment of a wide range of pulmonary diseases. Here we have developed a non-pathogenic chassis (CV8) of the human lung bacterium Mycoplasma pneumoniae (MPN) to treat lung diseases. We find that IL-10 expression by MPN has a limited impact on the lung inflammatory response in mice. To solve these issues, we rationally designed a single-chain IL-10 (SC-IL10) with or without surface mutations, using our protein design software (ModelX and FoldX). As compared to the IL-10 WT, the designed SC-IL10 molecules increase the effective expression in MPN four-fold, and the activity in mouse and human cell lines between 10 and 60 times, depending on the cell line. The SC-IL10 molecules expressed in the mouse lung by CV8 in vivo have a powerful anti-inflammatory effect on Pseudomonas aeruginosa lung infection. This rational design strategy could be used to other molecules with immunomodulatory properties used in bacterial therapy. |
DOI | 10.15252/msb.202211037 |
Alternate Journal | Mol Syst Biol |
PubMed ID | 36598022 |
PubMed Central ID | PMC9834763 |