{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:03:07Z","timestamp":1790809387570,"version":"4.1.0"},"reference-count":78,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,11,6]],"date-time":"2013-11-06T00:00:00Z","timestamp":1383696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Parasite Immunology"],"published-print":{"date-parts":[[2013,12]]},"abstract":"Summary<\/jats:title>L<\/jats:styled-content>eishmania major<\/jats:italic> is an aetiological agent of cutaneous leishmaniasis. The parasite primarily infects immune sentinel cells, specifically macrophages and dendritic cells, in the mammalian host. Infection is receptor mediated and is known to involve parasite binding to cell surface protein complement receptor 3 (CR<\/jats:styled-content>3, M<\/jats:styled-content>ac\u20101, CD<\/jats:styled-content>11b\/CD<\/jats:styled-content>18). Engagement of CR<\/jats:styled-content>3 by various ligands inhibits production of interleukin\u201012 (IL<\/jats:styled-content>\u201012), the cytokine that drives antileishmanial T<\/jats:styled-content> helper 1\u2010type immune responses. Likewise, L<\/jats:styled-content>.\u00a0major<\/jats:italic> infection inhibits IL<\/jats:styled-content>\u201012 production and activation of host macrophages. Our data indicate that in the absence of CR<\/jats:styled-content>3, L<\/jats:styled-content>.\u00a0major<\/jats:italic>\u2010infected bone marrow\u2010derived macrophages produce more IL<\/jats:styled-content>\u201012 and nitric oxide compared with WT<\/jats:styled-content> cells upon lipopolysaccharide (LPS<\/jats:styled-content>) stimulation. We therefore investigated multiple signalling pathways by which L.\u00a0major<\/jats:italic> may inhibit IL<\/jats:styled-content>\u201012 transcription through CR<\/jats:styled-content>3 ligation. We demonstrate that L.\u00a0major<\/jats:italic> infection does not elicit significant NF<\/jats:styled-content>\u03baB p65, MAPK<\/jats:styled-content>, IRF<\/jats:styled-content>\u20101 or IRF<\/jats:styled-content>\u20108 activation in WT<\/jats:styled-content> or CD<\/jats:styled-content>11b\u2010deficient macrophages. Furthermore, infection neither inhibits LPS<\/jats:styled-content>\u2010induced MAPK<\/jats:styled-content> or NF<\/jats:styled-content>\u03baB activation nor blocks IFN<\/jats:styled-content>\u2010\u03b3\u2010activated IRF<\/jats:styled-content>\u20101 and IRF<\/jats:styled-content>\u20108. ETS<\/jats:styled-content>\u2010mediated transcription, however, is inhibited by L<\/jats:styled-content>.\u00a0major<\/jats:italic> infection independently of CR<\/jats:styled-content>3. Our data indicate that L<\/jats:styled-content>.\u00a0major\u2010<\/jats:italic>mediated inhibition of IL<\/jats:styled-content>\u201012 occurs through CR<\/jats:styled-content>3 engagement; however, the mechanism of inhibition is independent of NF<\/jats:styled-content>\u03baB, MAPK<\/jats:styled-content>, IRF<\/jats:styled-content> and ETS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/pim.12049","type":"journal-article","created":{"date-parts":[[2013,7,8]],"date-time":"2013-07-08T15:40:16Z","timestamp":1373298016000},"page":"409-420","source":"Crossref","is-referenced-by-count":40,"title":["Leishmania major<\/i> inhibits IL<\/scp>\u201012 in macrophages by signalling through CR<\/scp>3 (CD<\/scp>11b\/CD<\/scp>18) and down\u2010regulation of ETS<\/scp>\u2010mediated transcription"],"prefix":"10.1111","volume":"35","author":[{"given":"C.","family":"Ricardo\u2010Carter","sequence":"first","affiliation":[{"name":"Eck Institute for Global Health Department of Biological Sciences University of Notre Dame Notre Dame IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Favila","sequence":"additional","affiliation":[{"name":"Eck Institute for Global Health Department of Biological Sciences University of Notre Dame Notre Dame IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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