PMID- 29162686 OWN - NLM STAT- MEDLINE DCOM- 20180627 LR - 20181113 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 114 IP - 49 DP - 2017 Dec 5 TI - Atypical activation of dendritic cells by Plasmodium falciparum. PG - E10568-E10577 LID - 10.1073/pnas.1708383114 [doi] AB - Dendritic cells (DCs) are activated by pathogens to initiate and shape immune responses. We found that the activation of DCs by Plasmodium falciparum, the main causative agent of human malaria, induces a highly unusual phenotype by which DCs up-regulate costimulatory molecules and secretion of chemokines, but not of cytokines typical of inflammatory responses (IL-1beta, IL-6, IL-10, TNF). Similar results were obtained with DCs obtained from malaria-naive US donors and malaria-experienced donors from Mali. Contact-dependent cross-talk between the main DC subsets, plasmacytoid and myeloid DCs (mDCs) was necessary for increased chemokine and IFN-alpha secretion in response to the parasite. Despite the absence of inflammatory cytokine secretion, mDCs incubated with P. falciparum-infected erythrocytes activated antigen-specific naive CD4(+) T cells to proliferate and secrete Th1-like cytokines. This unexpected response of human mDCs to P. falciparum exhibited a transcriptional program distinct from a classical LPS response, pointing to unique P. falciparum-induced activation pathways that may explain the uncharacteristic immune response to malaria. FAU - Gotz, Anton AU - Gotz A AD - Department of Microbiology, New York University School of Medicine, New York, NY 10016; anton.goetz@nih.gov ana.rodriguez@nyumc.org. AD - Laboratory of Immunogenetics, Malaria Infection Biology and Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852. FAU - Tang, Mei San AU - Tang MS AD - Department of Microbiology, New York University School of Medicine, New York, NY 10016. FAU - Ty, Maureen C AU - Ty MC AD - Department of Microbiology, New York University School of Medicine, New York, NY 10016. FAU - Arama, Charles AU - Arama C AD - Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique, and Technology of Bamako, 91094 Bamako, Mali. FAU - Ongoiba, Aissata AU - Ongoiba A AD - Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique, and Technology of Bamako, 91094 Bamako, Mali. FAU - Doumtabe, Didier AU - Doumtabe D AD - Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique, and Technology of Bamako, 91094 Bamako, Mali. FAU - Traore, Boubacar AU - Traore B AD - Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique, and Technology of Bamako, 91094 Bamako, Mali. FAU - Crompton, Peter D AU - Crompton PD AD - Laboratory of Immunogenetics, Malaria Infection Biology and Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852. FAU - Loke, P'ng AU - Loke P AD - Department of Microbiology, New York University School of Medicine, New York, NY 10016. FAU - Rodriguez, Ana AU - Rodriguez A AD - Department of Microbiology, New York University School of Medicine, New York, NY 10016; anton.goetz@nih.gov ana.rodriguez@nyumc.org. LA - eng GR - P30 CA016087/CA/NCI NIH HHS/United States GR - UL1 TR001445/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20171121 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Antigens, CD) RN - 0 (CCL2 protein, human) RN - 0 (CCL5 protein, human) RN - 0 (CXCL10 protein, human) RN - 0 (CXCL9 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL5) RN - 0 (Chemokine CXCL10) RN - 0 (Chemokine CXCL9) RN - 0 (HLA-DR Antigens) RN - 0 (IL10 protein, human) RN - 0 (IL1B protein, human) RN - 0 (IL6 protein, human) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Antigens, CD/genetics/immunology MH - CD4-Positive T-Lymphocytes/cytology/drug effects/*immunology MH - Chemokine CCL2/genetics/immunology MH - Chemokine CCL5/genetics/immunology MH - Chemokine CXCL10/genetics/immunology MH - Chemokine CXCL9/genetics/immunology MH - Coculture Techniques MH - Dendritic Cells/drug effects/*immunology/parasitology MH - Erythrocytes/*parasitology MH - Gene Expression Regulation MH - HLA-DR Antigens/genetics/immunology MH - *Host-Parasite Interactions MH - Humans MH - Interleukin-10/genetics/immunology MH - Interleukin-1beta/genetics/immunology MH - Interleukin-6/genetics/immunology MH - Lipopolysaccharides/pharmacology MH - *Lymphocyte Activation MH - Malaria, Falciparum/genetics/immunology/parasitology MH - Mali MH - Plasmodium falciparum/growth & development/*metabolism MH - Signal Transduction MH - Tumor Necrosis Factor-alpha/genetics/immunology PMC - PMC5724257 OTO - NOTNLM OT - Plasmodium falciparum OT - activation OT - cytokines OT - dendritic cells OT - malaria COIS- The authors declare no conflict of interest. EDAT- 2017/11/23 06:00 MHDA- 2018/06/28 06:00 PMCR- 2018/06/05 CRDT- 2017/11/23 06:00 PHST- 2017/11/23 06:00 [pubmed] PHST- 2018/06/28 06:00 [medline] PHST- 2017/11/23 06:00 [entrez] PHST- 2018/06/05 00:00 [pmc-release] AID - 1708383114 [pii] AID - 201708383 [pii] AID - 10.1073/pnas.1708383114 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):E10568-E10577. doi: 10.1073/pnas.1708383114. Epub 2017 Nov 21.