{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T13:11:16Z","timestamp":1649250676203},"reference-count":0,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,6]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>Monocyte dysfunction in helminth infection is one of the mechanisms proposed to explain the diminished parasite antigen-specific T cell responses seen with patent filarial infection. In fact, monocytes from filariae-infected individuals demonstrate internalized filarial antigens and, as a consequence, express inhibitory surface molecules and have diminished cytokine production. To investigate the mechanisms underlying monocyte dysfunction in filarial infections, purified human monocytes were exposed to live microfilariae (mf) of <jats:italic>Brugia malayi,<\/jats:italic> and the mRNA and protein expression of important inhibitory and\/or autophagy-related molecules were assessed. Our data indicate that mf-induced autophagy in human monocytes shown by the formation of autophagic vesicles, by the upregulation in the mRNA expression of autophagy-related genes <jats:italic>BCN1<\/jats:italic>, <jats:italic>LC3B<\/jats:italic>, <jats:italic>ATG5<\/jats:italic>, <jats:italic>ATG7<\/jats:italic> (<jats:italic>P<\/jats:italic> &lt; 0.05), and by increase in the levels of LC3B protein. Furthermore, this mf-induced autophagy increased the levels of monocyte CD206 expression. In addition, mf significantly induced the frequency of interferon (IFN)-\u03b3<jats:sup>+<\/jats:sup> human monocytes and at the same time induced the mRNA expression of indoleamine 2,3-dioxygenase (IDO) through an IFN-\u03b3-dependent mechanism; significantly enhanced tryptophan degradation (an indicator of IDO activity; <jats:italic>P<\/jats:italic> &lt; 0.005). Interestingly, this autophagy induction by mf in monocytes was IFN-\u03b3-dependent but IDO-independent as was reversed by anti-IFN-\u03b3 but not by an IDO inhibitor. Our data collectively suggest that mf of <jats:italic>Brugia malayi<\/jats:italic> regulate the function of monocytes by induction of IDO and IFN-\u03b3, induce autophagy through an IFN-\u03b3-dependent mechanism, and increase M2 phenotype through induction of autophagy; all acting in concert to drive monocyte dysfunction.<\/jats:p>","DOI":"10.4269\/ajtmh.21-1134","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T13:11:52Z","timestamp":1646053912000},"page":"1254-1262","source":"Crossref","is-referenced-by-count":0,"title":["Brugia malayi Microfilariae Induce Autophagy through an Interferon-\u03b3 Dependent Mechanism in Human Monocytes"],"prefix":"10.4269","volume":"106","author":[{"given":"Prakash Babu","family":"Narasimhan","sequence":"first","affiliation":[{"name":"1Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sameha","family":"Tariq","sequence":"additional","affiliation":[{"name":"1Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leor","family":"Akabas","sequence":"additional","affiliation":[{"name":"1Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Dorward","sequence":"additional","affiliation":[{"name":"2Microscopy Unit, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas B.","family":"Nutman","sequence":"additional","affiliation":[{"name":"1Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roshanak","family":"Tolouei Semnani","sequence":"additional","affiliation":[{"name":"1Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/106\/4\/article-p1254.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/106\/4\/article-p1254.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T12:38:50Z","timestamp":1649248730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/106\/4\/article-p1254.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,6]]},"references-count":0,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.21-1134","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,6]]}}}