{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:16:27Z","timestamp":1789578987509,"version":"build-2803163510"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Miliary tubersculosis (TB), an acute systemic blood disseminated tuberculosis mainly caused by <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>M. tuberculosis<\/jats:italic>), can cause signs of lymphopenia in clinical patients. To investigate whether\/how persistent mycobacteria antigen stimulation impairs hematopoiesis and the therapeutic effect of interleukin-7 (IL-7), a mouse model of Mycobacterium Bovis Bacillus Calmette-Gu\u00e9rin (BCG) intravenous infection with\/without an additional stimulation with <jats:italic>M. tuberculosis<\/jats:italic> multi-antigen cocktail containing ESAT6-CFP10 (EC) and Mtb10.4-HspX (MH) was established. Consistent with what happened in miliary TB, high dose of BCG intravenous infection with\/without additional antigen stimulation caused lymphopenia in peripheral blood. In which, the levels of cytokines IFN-\u03b3 and TNF-\u03b1 in serum increased, and consequently the expression levels of transcription factors <jats:italic>Batf2<\/jats:italic> and <jats:italic>IRF8<\/jats:italic> involved in myeloid differentiation were up-regulated, while the expression levels of transcription factors <jats:italic>GATA2<\/jats:italic> and <jats:italic>NOTCH1<\/jats:italic> involved in lymphoid commitment were down-regulated, and the proliferating activity of bone marrow (BM) lineage<jats:sup>-<\/jats:sup> c-Kit<jats:sup>+<\/jats:sup> (LK) cells decreased. Furthermore, recombinant Adeno-Associated Virus 2-mediated IL-7 (rAAV2-IL-7) treatment could significantly promote the elevation of BM lymphoid progenitors. It suggests that persistent mycobacteria antigen stimulation impaired lymphopoiesis of BM hematopoiesis, which could be restored by complement of IL-7.<\/jats:p>","DOI":"10.3389\/fcimb.2023.1079774","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T04:49:20Z","timestamp":1674017360000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Severe persistent mycobacteria antigen stimulation causes lymphopenia through impairing hematopoiesis"],"prefix":"10.3389","volume":"13","author":[{"given":"Fei","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyuan","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daquan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youjun","family":"Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingdong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.rmr.2012.08.008","article-title":"Pancytopenia: a severe complication of miliary tuberculosis","volume":"30","author":"Achi","year":"2013","journal-title":"Rev. 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