{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:56:52Z","timestamp":1791331012121,"version":"4.3.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although some studies indicate that the interaction of CD40 and CD40L is critical for IL-12 production and resistance to cutaneous leishmaniasis, others suggest that this pathway may be dispensable. In this article, we compared the outcome of Leishmania major infection in both CD40- and CD40L-deficient mice after treatment with rIL-12. We show that although CD40 and CD40L knockout (KO) mice are highly susceptible to L. major, treatment with rIL-12 during the first 2 wk of infection causes resolution of cutaneous lesions and control of parasite replication. Interestingly, although treated CD40 KO mice remained healed, developed long-term immunity, and were resistant to secondary L. major challenge, treated CD40L KO reactivated their lesion after cessation of rIL-12 treatment. Disease reactivation in CD40L KO mice was associated with impaired IL-12 and IFN-\u03b3 production and a concomitant increase in IL-4 production by cells from lymph nodes draining the infection site. We show that IL-12 production by dendritic cells and macrophages via CD40L\u2013macrophage Ag 1 (Mac-1) interaction is responsible for the sustained resistance in CD40 KO mice after cessation of rIL-12 treatment. Blockade of CD40L\u2013Mac-1 interaction with anti\u2013Mac-1 mAb led to spontaneous disease reactivation in healed CD40 KO mice, which was associated with impaired IFN-\u03b3 response and loss of infection-induced immunity after secondary L. major challenge. Collectively, our data reveal a novel role of CD40L\u2013Mac-1 interaction in IL-12 production, development, and maintenance of optimal Th1 immunity in mice infected with L. major.<\/jats:p>","DOI":"10.4049\/jimmunol.1500922","type":"journal-article","created":{"date-parts":[[2015,8,24]],"date-time":"2015-08-24T21:33:55Z","timestamp":1440452035000},"page":"3218-3226","source":"Crossref","is-referenced-by-count":17,"title":["Interaction of Macrophage Antigen 1 and CD40 Ligand Leads to IL-12 Production and Resistance in CD40-Deficient Mice Infected with\n                    <i>Leishmania major<\/i>"],"prefix":"10.1093","volume":"195","author":[{"given":"Ifeoma","family":"Okwor","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, University of Manitoba , Winnipeg, Manitoba R3E 0J9 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jude E","family":"Uzonna","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Manitoba , Winnipeg, Manitoba R3E 0J9 ,","place":["Canada"]},{"name":"Department of Immunology, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,10,1]]},"reference":[{"key":"2025030704164742100_r1","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.it.2011.10.004","article-title":"TNF superfamily in inflammatory disease: translating basic insights","volume":"33","author":"Croft","year":"2012","journal-title":"Trends Immunol."},{"key":"2025030704164742100_r2","doi-asserted-by":"crossref","first-page":"5858","DOI":"10.4049\/jimmunol.164.11.5858","article-title":"IL-12p70 production by Leishmania major-harboring human dendritic cells is a CD40\/CD40 ligand-dependent process","volume":"164","author":"Marovich","year":"2000","journal-title":"J. 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