PMID- 30804103 OWN - NLM STAT- MEDLINE DCOM- 20190916 LR - 20200309 IS - 1098-5522 (Electronic) IS - 0019-9567 (Print) IS - 0019-9567 (Linking) VI - 87 IP - 5 DP - 2019 Mar TI - Leishmania donovani Lipophosphoglycan Increases Macrophage-Dependent Chemotaxis of CXCR6-Expressing Cells via CXCL16 Induction. LID - 10.1128/IAI.00064-19 [doi] LID - e00064-19 AB - CXCL16 is a multifunctional chemokine that is highly expressed by macrophages and other immune cells in response to bacterial and viral pathogens; however, little is known regarding the role of CXCL16 during parasitic infections. The protozoan parasite Leishmania donovani is the causative agent of visceral leishmaniasis. Even though chemokine production is a host defense mechanism during infection, subversion of the host chemokine system constitutes a survival strategy adopted by the parasite. Here, we report that L. donovani promastigotes upregulate CXCL16 synthesis and secretion by bone marrow-derived macrophages (BMDM). In contrast to wild-type parasites, a strain deficient in the virulence factor lipophosphoglycan (LPG) failed to induce CXCL16 production. Consistent with this, cell treatment with purified L. donovani LPG augmented CXCL16 expression and secretion. Notably, the ability of BMDM to promote migration of cells expressing CXCR6, the cognate receptor of CXCL16, was augmented upon L. donovani infection in a CXCL16- and LPG-dependent manner. Mechanistically, CXCL16 induction by L. donovani required the activity of AKT and the mechanistic target of rapamycin (mTOR) but was independent of Toll-like receptor signaling. Collectively, these data provide evidence that CXCL16 is part of the inflammatory response elicited by L. donovani LPG in vitro Further investigation using CXCL16 knockout mice is required to determine whether this chemokine contributes to the pathogenesis of visceral leishmaniasis and to elucidate the underlying molecular mechanisms. CI - Copyright (c) 2019 American Society for Microbiology. FAU - Chaparro, Visnu AU - Chaparro V AUID- ORCID: 0000-0001-6880-9234 AD - Institut National de la Recherche Scientifique-Institut Armand-Frappier, Laval, Quebec, Canada. FAU - Leroux, Louis-Philippe AU - Leroux LP AUID- ORCID: 0000-0002-9736-1827 AD - Institut National de la Recherche Scientifique-Institut Armand-Frappier, Laval, Quebec, Canada. FAU - Zimmermann, Aude AU - Zimmermann A AD - Institut National de la Recherche Scientifique-Institut Armand-Frappier, Laval, Quebec, Canada. FAU - Jardim, Armando AU - Jardim A AD - Institute of Parasitology, McGill University, Sainte-Anne-de-Bellevue, Quebec, Canada. FAU - Johnston, Brent AU - Johnston B AD - Departments of Microbiology and Immunology and Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada. FAU - Descoteaux, Albert AU - Descoteaux A AUID- ORCID: 0000-0002-0633-5309 AD - Institut National de la Recherche Scientifique-Institut Armand-Frappier, Laval, Quebec, Canada. FAU - Jaramillo, Maritza AU - Jaramillo M AUID- ORCID: 0000-0002-1910-5684 AD - Institut National de la Recherche Scientifique-Institut Armand-Frappier, Laval, Quebec, Canada maritza.jaramillo@iaf.inrs.ca. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190423 PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Chemokine CXCL16) RN - 0 (Glycosphingolipids) RN - 0 (lipophosphonoglycan) SB - IM MH - Animals MH - Chemokine CXCL16/*immunology MH - Chemotaxis/*immunology MH - Disease Models, Animal MH - Glycosphingolipids/*immunology MH - Host-Parasite Interactions/*immunology MH - Humans MH - Leishmania donovani/*immunology MH - Leishmaniasis, Visceral/*immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL PMC - PMC6479025 OTO - NOTNLM OT - CXCL16 OT - Leishmania OT - cell signaling OT - chemokine OT - inflammation OT - lipophosphoglycan OT - macrophage EDAT- 2019/02/26 06:00 MHDA- 2019/09/17 06:00 PMCR- 2019/10/23 CRDT- 2019/02/27 06:00 PHST- 2019/01/28 00:00 [received] PHST- 2019/02/18 00:00 [accepted] PHST- 2019/02/26 06:00 [pubmed] PHST- 2019/09/17 06:00 [medline] PHST- 2019/02/27 06:00 [entrez] PHST- 2019/10/23 00:00 [pmc-release] AID - IAI.00064-19 [pii] AID - 00064-19 [pii] AID - 10.1128/IAI.00064-19 [doi] PST - epublish SO - Infect Immun. 2019 Apr 23;87(5):e00064-19. doi: 10.1128/IAI.00064-19. Print 2019 Mar.