Atypical activation of dendritic cells by Plasmodium falciparum .

Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE

Original Publication: Washington, DC : National Academy of Sciences

Host-Parasite Interactions* ; Lymphocyte Activation*; CD4-Positive T-Lymphocytes/*immunology ; Dendritic Cells/*immunology ; Erythrocytes/*parasitology ; Plasmodium falciparum/*metabolism; Antigens, CD/genetics ; Antigens, CD/immunology ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/drug effects ; Chemokine CCL2/genetics ; Chemokine CCL2/immunology ; Chemokine CCL5/genetics ; Chemokine CCL5/immunology ; Chemokine CXCL10/genetics ; Chemokine CXCL10/immunology ; Chemokine CXCL9/genetics ; Chemokine CXCL9/immunology ; Coculture Techniques ; Dendritic Cells/drug effects ; Dendritic Cells/parasitology ; Gene Expression Regulation ; HLA-DR Antigens/genetics ; HLA-DR Antigens/immunology ; Humans ; Interleukin-10/genetics ; Interleukin-10/immunology ; Interleukin-1beta/genetics ; Interleukin-1beta/immunology ; Interleukin-6/genetics ; Interleukin-6/immunology ; Lipopolysaccharides/pharmacology ; Malaria, Falciparum/genetics ; Malaria, Falciparum/immunology ; Malaria, Falciparum/parasitology ; Mali ; Plasmodium falciparum/growth & development ; Signal Transduction ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/immunology

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-1β, IL-6, IL-10, TNF). Similar results were obtained with DCs obtained from malaria-naïve 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-α secretion in response to the parasite. Despite the absence of inflammatory cytokine secretion, mDCs incubated with P. falciparum -infected erythrocytes activated antigen-specific naïve 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.
Competing Interests: The authors declare no conflict of interest.

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P30 CA016087 United States CA NCI NIH HHS; UL1 TR001445 United States TR NCATS NIH HHS

Keywords: Plasmodium falciparum; activation; cytokines; dendritic cells; malaria

0 (Antigens, CD)
0 (CCL2 protein, human)
0 (CCL5 protein, human)
0 (CXCL10 protein, human)
0 (CXCL9 protein, human)
0 (Chemokine CCL2)
0 (Chemokine CCL5)
0 (Chemokine CXCL10)
0 (Chemokine CXCL9)
0 (HLA-DR Antigens)
0 (IL10 protein, human)
0 (IL1B protein, human)
0 (IL6 protein, human)
0 (Interleukin-1beta)
0 (Interleukin-6)
0 (Lipopolysaccharides)
0 (Tumor Necrosis Factor-alpha)
130068-27-8 (Interleukin-10)

Date Created: 20171123 Date Completed: 20180627 Latest Revision: 20181113

20221213

PMC5724257

10.1073/pnas.1708383114

29162686