{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T05:45:01Z","timestamp":1774849501682,"version":"3.50.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Congenital tuberculosis (CTB) is a rare and life-threatening condition with a mortality rate of approximately 53% even with clinical intervention, which is markedly higher than that of adult tuberculosis (ATB). To date, the phenotypic and functional characteristics of immune cells in CTB neonates remain largely uncharacterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this case-control study, we enrolled nine CTB neonates and nine paired healthy control (pHC) neonates, collecting basic clinical characteristics of the infants and their mothers, and comparing routine blood test results, C-reactive protein (CRP) levels, and lymphocyte subset profiles via flow cytometry during hospitalization. For exploratory mechanistic investigation, we performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells isolated from one pHC neonate and one CTB neonate at the pre-symptomatic early stage, with additional scRNA-seq data of one ATB patient included for comparative analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At the clinical level, CTB neonates exhibited gradual lymphocyte depletion, reduced regulatory T (Treg) cell frequency, and an excessive innate immune response-changes that may drive an overwhelming pro-inflammatory response alongside a compromised adaptive immune response. Exploratory scRNA-seq analysis of the single CTB and pHC neonate revealed a general suppression of immune function in T and natural killer (NK) cells in CTB. T cell subset transcriptomic profiling further showed decreased proportions of Tregs, Th1\/17 cells, proliferating T cells, and cytotoxic CD8+ T cells in the CTB neonate, with a concomitant reduction in cytotoxic NK cell frequency. The proportion of myeloid cell subsets in CTB was similar to that in HCs, however, myeloid cells in CTB showed a generally activated inflammatory response. Compared with ATB, myeloid cells of CTB expressed high levels of inflammatory markers. Transcriptomic features of  T and NK cell function in the CTB neonate were similar to those in the ATB patient, yet these immune cells in the CTB neonate showed a generally weaker antigen presentation capacity. These preliminary features may partially underpin the high mortality of CTB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Notably, the scRNA-seq findings presented here are exploratory and hypothesis-generating, and should be interpreted with caution. Further studies with expanded scRNA-seq cohorts are urgently needed to validate these initial observations and elucidate the core immune pathophysiological mechanisms of CTB.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1614510","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T04:12:55Z","timestamp":1774843975000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunopathological signatures in congenital tuberculosis-a case-matched study"],"prefix":"10.3389","volume":"17","author":[{"given":"Ren","family":"Zhuxiao","sequence":"first","affiliation":[{"name":"Department of Neonatology, Guangdong Women and Children Hospital, Southern University of Science and Technology","place":["Guangzhou, China"]},{"name":"Department of neonatology, Guangdong Neonatal Intensive care unit (ICU) Medical Quality Control Center","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhang","family":"Shandan","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Maternal and Child Health Care Hospital of HuaDu District, Guangdong Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Chunhui","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Zhongshan Boai Hospital","place":["Zhongshan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mo","family":"Wenhui","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Foshan Fosun Chancheng Hospital","place":["Foshan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Guangdong Women and Children Hospital, Southern University of Science and Technology","place":["Guangzhou, 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