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HTLV-1 and<jats:italic>Strongyloides stercoralis<\/jats:italic>are co-endemic throughout much of their worldwide ranges resulting in a significant incidence of coinfection. Independently, HTLV-1 induces a Th1 response and<jats:italic>S<\/jats:italic>.<jats:italic>stercoralis<\/jats:italic>infection induces a Th2 response. However, coinfection with the two pathogens has been associated with the development of<jats:italic>S<\/jats:italic>.<jats:italic>stercoralis<\/jats:italic>hyperinfection and an alteration of the Th1\/Th2 balance. In this study, a model of HTLV-1 and<jats:italic>S<\/jats:italic>.<jats:italic>stercoralis<\/jats:italic>coinfection in CD34<jats:sup>+<\/jats:sup>umbilical cord blood hematopoietic stem cell engrafted humanized mice was established. An increased level of mortality was observed in the HTLV-1 and coinfected animals when compared to the<jats:italic>S<\/jats:italic>.<jats:italic>stercoralis<\/jats:italic>infected group. The mortality was not correlated with proviral loads or total viral RNA. Analysis of cytokine profiles showed a distinct shift towards Th1 responses in HTLV-1 infected animals, a shift towards Th2 cytokines in<jats:italic>S<\/jats:italic>.<jats:italic>stercoralis<\/jats:italic>infected animals and elevated TNF-\u03b1 responses in coinfected animals. HTLV-1 infected and coinfection groups showed a significant, yet non-clonal expansion of the CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>T-cell population. Numbers of worms in the coinfection group did not differ from those of the<jats:italic>S<\/jats:italic>.<jats:italic>stercoralis<\/jats:italic>infected group and no autoinfective larvae were found. However, infective larvae recovered from the coinfection group showed an enhancement in growth, as was seen in mice with<jats:italic>S<\/jats:italic>.<jats:italic>stercoralis<\/jats:italic>hyperinfection caused by treatment with steroids. Humanized mice coinfected with<jats:italic>S<\/jats:italic>.<jats:italic>stercoralis<\/jats:italic>and HTLV-1 demonstrate features associated with human infection with these pathogens and provide a unique opportunity to study the interaction between these two infections<jats:italic>in vivo<\/jats:italic>in the context of human immune cells.<\/jats:p>","DOI":"10.1371\/journal.pntd.0009559","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T17:28:11Z","timestamp":1627406891000},"page":"e0009559","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Strongyloides stercoralis and HTLV-1 coinfection in CD34+ cord blood stem cell humanized mice: Alteration of cytokine responses and enhancement of larval growth"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7322-4994","authenticated-orcid":true,"given":"Lauren E.","family":"Springer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Patton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9971-4844","authenticated-orcid":true,"given":"Tingting","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold B.","family":"Rabson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Ching","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Manser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7611-8211","authenticated-orcid":true,"given":"James B.","family":"Lok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Hess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3072-2541","authenticated-orcid":true,"given":"David","family":"Abraham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"issue":"5","key":"pntd.0009559.ref001","doi-asserted-by":"crossref","first-page":"e2214","DOI":"10.1371\/journal.pntd.0002214","article-title":"Strongyloides stercoralis: a plea for action","volume":"7","author":"Z Bisoffi","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"issue":"7","key":"pntd.0009559.ref002","doi-asserted-by":"crossref","first-page":"e2288","DOI":"10.1371\/journal.pntd.0002288","article-title":"Strongyloides stercoralis: Global Distribution and Risk Factors","volume":"7","author":"F Schar","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"pntd.0009559.ref003","first-page":"194","article-title":"Strongyloidiasis","volume":"7","author":"S Ganesh","year":"2011","journal-title":"Gastroenterol Hepatol [N Y]"},{"issue":"1","key":"pntd.0009559.ref004","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1073\/pnas.1712235114","article-title":"Methylprednisolone acetate induces, and \u03947-dafachronic acid suppresses, Strongyloides stercoralis hyperinfection in NSG mice","volume":"115","author":"JB Patton","year":"2018","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"pntd.0009559.ref005","doi-asserted-by":"crossref","first-page":"f4610","DOI":"10.1136\/bmj.f4610","article-title":"Strongyloides stercoralis infection","volume":"347","author":"D Greaves","year":"2013","journal-title":"BMJ"},{"issue":"2","key":"pntd.0009559.ref006","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s12639-019-01090-x","article-title":"Strongyloides stercoralis hyperinfection syndrome: a deeper understanding of a neglected disease","volume":"43","author":"G Vasquez-Rios","year":"2019","journal-title":"J Parasit Dis"},{"issue":"1","key":"pntd.0009559.ref007","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.idc.2018.10.006","article-title":"Strongyloidiasis: A Neglected Tropical Disease","volume":"33","author":"A Krolewiecki","year":"2019","journal-title":"Infect Dis Clin North Am"},{"key":"pntd.0009559.ref008","first-page":"388","article-title":"Epidemiological Aspects and World Distribution of HTLV-1","volume":"3","author":"A Gessain","year":"2012","journal-title":"Infection. 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