{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T03:15:01Z","timestamp":1780629301908,"version":"3.54.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:p>Vitamin D is a key regulator in calcium and phosphorus metabolism which are essential for maintaining bone health. Recent reports also showed a role for vitamin D in immune regulation which may be linked to vitamin D deficiency in autoimmune disorders including inflammatory diseases and Crohn\u2019s disease (CD). This study examines the role of vitamin D deficiency in the regulation of Cathelicidin Antimicrobial Peptide (<jats:italic>CAMP<\/jats:italic>) in CD-like macrophages. The latter includes macrophages infected with <jats:italic>Mycobacterium avium<\/jats:italic> subsp. <jats:italic>paratuberculosis<\/jats:italic> (MAP) isolated from CD patient. Initially, we measured cathelicidin and calcitriol in <jats:italic>ex vivo<\/jats:italic> plasma samples from CD patients with or without MAP infection (<jats:italic>N=40<\/jats:italic> per group). We also measured the expression and production of <jats:italic>CAMP<\/jats:italic>\/LL-37, TNF-\u03b1, IL-1\u03b2, IL-10, cellular oxidative stress markers, and bacterial viability following treatment of MAP-infected macrophages with four different forms of vitamin D (D2, D3, calcifediol, and calcitriol). From these studies, we determined that LL-37 and calcitriol were significantly lower in CD samples from MAP-positive patients [155.55 \u00b1 49.77 ng\/mL and 51.48 \u00b1 31.04 pg\/mL, respectively] compared to MAP-negative patients [193.01 \u00b1 78.95 ng\/mL and 272.36 \u00b1 94.77 pg\/mL, respectively]. Moreover, calcitriol and calcifediol upregulated <jats:italic>CAMP<\/jats:italic> expression by nearly 5-fold and 3-fold, respectively. However, following MAP infection, only calcitriol increased <jats:italic>CAMP<\/jats:italic> by 3-folds. Both calcitriol and LL-37 reduced intracellular MAP viability by ~3 folds and inhibited TNF-\u03b1 and IL-1\u03b2 expression and production in these cells. Treating co-culture of Caco-2 monolayers and MAP-infected macrophages with LL-37 or calcitriol have shown a reduction in <jats:italic>NOX-1<\/jats:italic> expression and DHE signal, in addition to a higher NADPH\/NADPt ratio. Notably, calcitriol\u2019s anti-inflammatory effects were lost upon <jats:italic>CAMP<\/jats:italic> knockdown by CAMP-siRNA transfection. Altogether, the data indicate that MAP infection and burden is significant in CD by disrupting the conversion of calcifediol to calcitriol and downregulation of <jats:italic>CAMP<\/jats:italic> expression leading to vitamin D deficiency.<\/jats:p>","DOI":"10.3389\/fcimb.2022.875772","type":"journal-article","created":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T08:10:04Z","timestamp":1649059804000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Cathelicidin Mediates an Anti-Inflammatory Role of Active Vitamin D (Calcitriol) During M. paratuberculosis Infection"],"prefix":"10.3389","volume":"12","author":[{"given":"Joseph A.","family":"Vaccaro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Qasem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh A.","family":"Naser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.jsbmb.2013.12.009","article-title":"Regulation of the Extrarenal CYP27B1-Hydroxylase","author":"Adams","year":"2014","journal-title":"J. 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