University of Massachusetts 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.

Comments

This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.

Journal/Book/Conference Title

bioRxiv

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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