UMass Chan Medical School Faculty Publications
UMMS Affiliation
Department of Microbiology and Physiological Systems
Publication Date
2021-02-24
Document Type
Article Preprint
Disciplines
Bacteria | Immunology of Infectious Disease | Microbiology
Abstract
Disseminated infection with the high virulence strain of Mycobacterium avium 25291 lead to progressive thymic atrophy. We previously uncovered that M. avium-induced thymic atrophy is due to increased levels of glucocorticoids synergizing with nitric oxide (NO) produced by interferon gamma (IFNγ) activated macrophages. Where and how these mediators are playing, was yet to be understood. We hypothesized that IFNγ and NO might be affecting bone marrow (BM) T cell precursors and/or T cell differentiation in the thymus. We show that M. avium infection causes a reduction on the percentage of lymphoid-primed multipotent progenitors (LMPP) and common lymphoid progenitors (CLP). Additionally, BM precursors from infected mice are unable to reconstitute thymi of RAGKO mice in an IFNγ-dependent way. Thymi from infected mice presents a NO-dependent inflammation. When transplanted under the kidney capsule of non-infected mice, thymic stroma from infected mice is unable to sustain T cell differentiation. Finally, we observed increased thymocyte death via apoptosis after infection, independent of both IFNγ and iNOS, and a decrease on activated caspase-3 positive thymocytes, that was not observed in the absence of iNOS expression. Together our data suggests that M. avium-induced thymic atrophy results from a combination of impairments, mediated by IFNγ and NO, affecting different steps of T cell differentiation from T cell precursor cells in the BM to the thymic stroma and thymocytes.
Keywords
Immunology, thymic atrophy, Mycobacterium avium
Rights and Permissions
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
10.1101/2021.02.23.432464
Source
bioRxiv 2021.02.23.432464; doi: https://doi.org/10.1101/2021.02.23.432464. Link to preprint on bioRxiv.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Barreira-Silva P, Melo-Miranda R, Nobrega C, Roque S, Serre-Miranda C, Borges M, de Sá Calçada D, Behar SM, Appelberg R, Correia-Neves M. (2021). IFNγ and iNOS-mediated alterations in the bone marrow and thymus and its impact on Mycobacterium avium-induced thymic atrophy [preprint]. UMass Chan Medical School Faculty Publications. https://doi.org/10.1101/2021.02.23.432464. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1929
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.