{"id":28782,"date":"2025-04-03T06:49:29","date_gmt":"2025-04-03T04:49:29","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/04\/03\/bcg-induced-innate-immune-response-heterogeneity-and-susceptibility-to-pediatric-tuberculosis\/"},"modified":"2025-04-03T06:49:29","modified_gmt":"2025-04-03T04:49:29","slug":"bcg-induced-innate-immune-response-heterogeneity-and-susceptibility-to-pediatric-tuberculosis","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/04\/03\/bcg-induced-innate-immune-response-heterogeneity-and-susceptibility-to-pediatric-tuberculosis\/","title":{"rendered":"BCG induced innate immune response heterogeneity and susceptibility to pediatric tuberculosis"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Apr 2:vkae062. doi: 10.1093\/jimmun\/vkae062. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Although immune responses to bacillus Calmette-Guerin (BCG)-vaccination and susceptibility to pediatric tuberculosis (TB) vary across individuals, the underlying cellular mechanism regulating this heterogeneity is poorly understood. We used a nested case-control study with a 2-yr prospective observation period to examine whether genetic variation is associated with BCG-induced innate immune responses and susceptibility to pediatric TB (N = 134 cases, 516 controls) in BCG-vaccinated infants. Whole blood collected at 10 wk of age from 189 control infants was stimulated with BCG or media and examined with flow cytometry to measure BCG-induced PDL1, CD40, and cytokine expression in myeloid (mDC) and plasmacytoid (pDC) dendritic cells, monocytes, and neutrophils. We used a cellular and clinical GWAS to assess for associations between genetic variants, BCG-induced innate immune responses, and susceptibility to TB. We identified 11 lead genetic variants at genome-wide level significance associated with BCG-induced cytokine and surface expression markers including PDL1 (5 pDCs, 3 mDCs, 1 monocytes), CD40 (1 mDCs), and IL-6 (1 monocytes). An IGLL1 variant (rs2096522) was associated with mDC CD40 expression (P = 1.6e-08) and was also discovered as a significant variant using a gene-based method. In the clinical GWAS, we identified 39 lead variants mapping to 74 genes suggestive of an association with susceptibility to pediatric TB (P &lt; 1e-05), but no variant reached genome-wide significance. One clinical lead variant in the PDE8A region (rs1023844, P = 9.6e-07) was also an eQTL and associated with BCG-induced monocyte PDL1 expression. In summary, we identified genetic variants associated with heterogeneity in infant BCG-induced innate immune responses with potential immunoregulatory mechanisms.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40174917\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250403004928&amp;v=2.18.0.post9+e462414\">40174917<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkae062\">10.1093\/jimmun\/vkae062<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Apr 2:vkae062. doi: 10.1093\/jimmun\/vkae062. Online ahead of print. ABSTRACT Although immune responses to bacillus Calmette-Guerin (BCG)-vaccination and susceptibility to pediatric tuberculosis (TB) vary across individuals, the underlying cellular mechanism regulating this heterogeneity is poorly understood. We used a nested case-control study with a 2-yr prospective observation period to examine whether genetic variation &#8230; <a title=\"BCG induced innate immune response heterogeneity and susceptibility to pediatric tuberculosis\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/04\/03\/bcg-induced-innate-immune-response-heterogeneity-and-susceptibility-to-pediatric-tuberculosis\/\" aria-label=\"Read more about BCG induced innate immune response heterogeneity and susceptibility to pediatric tuberculosis\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-28782","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/28782","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=28782"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/28782\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=28782"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=28782"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=28782"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}