{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T08:37:46Z","timestamp":1775205466318,"version":"3.50.1"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2015,11,17]],"date-time":"2015-11-17T00:00:00Z","timestamp":1447718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2015,12,31]],"date-time":"2015-12-31T00:00:00Z","timestamp":1451520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2015,12,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>High levels of circulating immunocomplexes (ICs) are found in patients with either infectious or sterile inflammation. We report that patients with either<jats:named-content content-type=\"genus-species\">Plasmodium falciparum<\/jats:named-content>or<jats:named-content content-type=\"genus-species\">Plasmodium vivax<\/jats:named-content>malaria have increased levels of circulating anti-DNA antibodies and ICs containing parasite DNA. Upon stimulation with malaria-induced ICs, monocytes express an NF-\u03baB transcriptional signature. The main source of IC-induced proinflammatory cytokines (i.e., tumor necrosis factor alpha [TNF-\u03b1] and interleukin-1\u03b2 [IL-1\u03b2])in peripheral blood mononuclear cells from acute malaria patients was found to be a CD14<jats:sup>+<\/jats:sup>CD16 (Fc\u03b3RIIIA)<jats:sup>+<\/jats:sup>CD64 (Fc\u03b3RI)<jats:sup>high<\/jats:sup>CD32 (Fc\u03b3RIIB)<jats:sup>low<\/jats:sup>monocyte subset. Monocytes from convalescent patients were predominantly of the classical phenotype (CD14<jats:sup>+<\/jats:sup>CD16<jats:sup>\u2212<\/jats:sup>) that produces high levels of IL-10 and lower levels of TNF-\u03b1 and IL-1\u03b2 in response to ICs. Finally, we report a novel role for the proinflammatory activity of ICs by demonstrating their ability to induce inflammasome assembly and caspase-1 activation in human monocytes. These findings illuminate our understanding of the pathogenic role of ICs and monocyte subsets and may be relevant for future development of immunity-based interventions with broad applications to systemic inflammatory diseases.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Every year, there are approximately 200 million cases of<jats:named-content content-type=\"genus-species\">Plasmodium falciparum<\/jats:named-content>and<jats:named-content content-type=\"genus-species\">P. vivax<\/jats:named-content>malaria, resulting in nearly 1 million deaths, most of which are children. Decades of research on malaria pathogenesis have established that the clinical manifestations are often a consequence of the systemic inflammation elicited by the parasite. Recent studies indicate that parasite DNA is a main proinflammatory component during infection with different<jats:italic>Plasmodium<\/jats:italic>species. This finding resembles the mechanism of disease in systemic lupus erythematosus, where host DNA plays a central role in stimulating an inflammatory process and self-damaging reactions. In this study, we disclose the mechanism by which ICs containing<jats:italic>Plasmodium<\/jats:italic>DNA activate innate immune cells and consequently stimulate systemic inflammation during acute episodes of malaria. Our results further suggest that Toll-like receptors and inflammasomes have a central role in malaria pathogenesis and provide new insights toward developing novel therapeutic interventions for this devastating disease.<\/jats:p>","DOI":"10.1128\/mbio.01605-15","type":"journal-article","created":{"date-parts":[[2015,11,18]],"date-time":"2015-11-18T01:58:07Z","timestamp":1447811887000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["DNA-Containing Immunocomplexes Promote Inflammasome Assembly and Release of Pyrogenic Cytokines by CD14<sup>+<\/sup>CD16<sup>+<\/sup>CD64<sup>high<\/sup>CD32<sup>low<\/sup>Inflammatory Monocytes from Malaria Patients"],"prefix":"10.1128","volume":"6","author":[{"given":"Isabella C.","family":"Hirako","sequence":"first","affiliation":[{"name":"Centro de Pesquisa Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil"}]},{"given":"Carolina","family":"Gallego-Marin","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"},{"name":"Centro Internacional de Entrenamiento e Investigaciones Medicas-CIDEIM, Cali, Colombia"}]},{"given":"Marco A.","family":"Ataide","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil"},{"name":"Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"}]},{"given":"Warrison A.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil"},{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, 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