Integrative analysis of microRNA and mRNA expression profiles of monocyte- derived dendritic cells differentiation during experimental cerebral malaria

Heterogeneity and high plasticity are common features of cells from the mononuclear phagocyte system: monocytes (MOs), macrophages, and dendritic cells (DCs). Upon activation by microbial agents, MO can differentiate into MO- derived DCs (MODCs). In previous work, we have shown that during acute infection with Plasmodium berghei ANKA (PbA), MODCs become, transiently, the main CD11b+ myeloid population in the spleen (SP) and once recruited to the brain play an important role in the development of experimental cerebral malaria (ECM). Here, we isolated 4 cell populations: bone marrow (BM) MOs (BM- MOs) and SP- MOs from uninfected mice; BM inflammatory MOs (BM- iMOs) and SP- MODCs from PbA- infected mice and used a system biology approach to a holistic transcriptomic comparison and provide an interactome analysis by integrating differentially expressed miRNAs (DEMs) and their differentially expressed gene targets (DEGs) data. The Jaccard index (JI) was used for gauging the similarity and diversity among these cell populations. Whereas BM- MOs, BM- iMOs, and SP- MOs presented high similarity of DEGs, SP- MODCs distinguished by showing a greater number of DEGs. Moreover, functional analysis identified an enrichment in canonical pathways, such as DC maturation, neuroinflammation, and IFN signaling. Upstream regulator analysis identified IFNγ as the potential upstream molecule that can explain the observed DEMs- Target DEGs intersections in SP- MODCs. Finally, directed target analysis and in vivo/ex vivo assays indicate that SP- MODCs differentiate in the SP and IFNγ is a main driver of this process.Graphical AbstractInteractome analysis between miRNAs and their target genes in IFNγ- mediated differentiation of splenic MODCs during Plasmodium infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162711/1/jlb10625-sup-0002-TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162711/6/jlb10625-sup-0001-FigureS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162711/5/jlb10625.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162711/4/jlb10625_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162711/3/jlb10625-sup-0004-TableS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162711/2/jlb10625-sup-0003-TableS2.pd

Neutrophil Paralysis in Plasmodium vivax Malaria

Plasmodium vivax is responsible for approximately 60–80% of the malaria cases in the world, and contributes to significant social and economic instability in the developing countries of Latin America and Asia. The pathogenesis of P. vivax malaria is a consequence of host derived inflammatory mediators. Hence, a better understanding of the mechanisms involved in induction of systemic inflammation during P. vivax malaria is critical for the clinical management and prevention of severe disease. The innate immune receptors recognize Plasmodium sp. and initiate a broad spectrum of host defense mechanisms that mediate resistance to infection. However, the innate immune response is the classic “two-edged sword”, and clinical malaria is associated with high levels of circulating pro-inflammatory cytokines. Our findings show that both monocytes and neutrophils are highly activated during malaria. Monocytes produced high levels of IL-1β, IL-6 and TNF-α during acute malaria. On the other hand, neutrophils were a poor source of cytokines, but displayed an enhanced phagocytic activity and superoxide production. Unexpectedly, we noticed an impaired chemotaxis of neutrophils towards an IL-8 (CXCL8) gradient. We proposed that neutrophil paralysis is in part responsible for the enhanced susceptibility to bacterial infection observed in malaria patients

Requirement of UNC93B1 reveals a critical role for TLR7 in host resistance to primary infection with Trypanosoma cruzi

Submitted by Nuzia Santos ([email protected]) on 2014-08-04T18:55:42Z No. of bitstreams: 1 Requirement of UNC93B1 reveals a critical role for TLR7 in host resistance to primary infection with Trypanosoma cruzi.pdf: 3284582 bytes, checksum: 67620ec691076cf2c5ad46a02c597c03 (MD5)Made available in DSpace on 2014-08-04T18:55:42Z (GMT). No. of bitstreams: 1 Requirement of UNC93B1 reveals a critical role for TLR7 in host resistance to primary infection with Trypanosoma cruzi.pdf: 3284582 bytes, checksum: 67620ec691076cf2c5ad46a02c597c03 (MD5) Previous issue date: 2011University of Massachusetts. Medical School. Division of Infectious Disease and Immunology.Worcester, MA, USAUniversity of Massachusetts. Medical School. Division of Infectious Disease and Immunology.Worcester, MA, USAUniversity of Massachusetts. Medical School. Division of Infectious Disease and Immunology.Worcester, MA, USAUniversity of Massachusetts. Medical School. Division of Infectious Disease and Immunology.Worcester, MA, USAUniversidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia e Departamento de Parasitologia. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia e Departamento de Parasitologia. Belo Horizonte, MG, BrazilUniversity of Massachusetts. Medical School. Division of Infectious Disease and Immunology.Worcester, MA, USAUniversity of Massachusetts. Medical School. Division of Infectious Disease and Immunology.Worcester, MA, USA/Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, BrasilUNC93B1 associates with Toll-Like Receptor (TLR) 3, 7 and 9, mediating their translocation from the endoplasmic reticulum to the endolysosome, thus allowing proper activation by microbial nucleic acids. We found that the triple deficient ‘3d’ mice, which lack functional UNC93B1 as well as functional endossomal TLRs, are highly susceptible to infection with Trypanosoma cruzi. The enhanced parasitemia and mortality in 3d animals were associated with impaired pro-inflammatory response, including reduced levels of IL-12p40 and IFN-γ. Importantly, the phenotype of 3d mice was intermediary between MyD88−/−(highly susceptible) and TLR9−/−(less susceptible), indicating the involvement of an additional UN93B1-dependent-TLR(s) on host resistance to T. cruzi. Hence, our experiments also revealed that TLR7 is a ritical innate immune receptor involved in recognition of parasite RNA, induction of IL-12p40 by dendritic cells, and consequent IFN-γby T lymphocytes. Furthermore, we show that upon T. cruzi infection triple TLR3/7/9−/−mice had similar phenotype than 3d mice. These data imply hat the nucleic acid-sensing TLRs are critical determinants of host resistance to primary infection with T. cruzi

Therapeutical targeting of nucleic acid-sensing Toll-like receptors prevents experimental cerebral malaria

Submitted by Nuzia Santos ([email protected]) on 2014-10-28T16:53:06Z No. of bitstreams: 1 Therapeutical targeting of nucleic acid-sensing Toll-like receptors prevents experimental cerebral malaria.pdf: 1304082 bytes, checksum: 32809b05c1e6bbae808d147ce8bcc16b (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2014-10-28T17:13:42Z (GMT) No. of bitstreams: 1 Therapeutical targeting of nucleic acid-sensing Toll-like receptors prevents experimental cerebral malaria.pdf: 1304082 bytes, checksum: 32809b05c1e6bbae808d147ce8bcc16b (MD5)Made available in DSpace on 2014-10-28T17:13:42Z (GMT). No. of bitstreams: 1 Therapeutical targeting of nucleic acid-sensing Toll-like receptors prevents experimental cerebral malaria.pdf: 1304082 bytes, checksum: 32809b05c1e6bbae808d147ce8bcc16b (MD5) Previous issue date: 2011Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil/University of Massachusetts. Medical School. Department of Medicine. Division of Infectious Diseases and Immunology. Worcester, MAEisai Research Institute. Andover, MAEisai Research Institute. Andover, MAEisai Research Institute. Andover, MAEisai Research Institute. Andover, MAEisai Research Institute. Andover, MAEisai Research Institute. Andover, MAFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquimica e Imunologia. Belo Horizonte, MG, BrazilExcessive release of proinflammatory cytokines by innate immune cells is an important component of the pathogenic basis of malaria. Proinflammatory cytokines are a direct output of Toll-like receptor (TLR) activation during microbial infection. Thus, interference with TLR function is likely to render a better clinical outcome by preventing their aberrant activation and the excessive release of inflammatory mediators. Herein, we describe the protective effect and mechanism of action of E6446, a synthetic antagonist of nucleic acid-sensing TLRs, on experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA. We show that in vitro, low doses of E6446 specifically inhibited the activation of human and mouse TLR9. Tenfold higher concentrations of this compound also inhibited the human TLR8 response to single-stranded RNA. In vivo, therapy with E6446 diminished the activation of TLR9 and prevented the exacerbated cytokine response observed during acute Plasmodium infection. Furthermore, severe signs of ECM, such as limb paralysis, brain vascular leak, and death, were all prevented by oral treatment with E6446. Hence, we provide evidence that supports the involvement of nucleic acid-sensing TLRs in malaria pathogenesis and that interference with the activation of these receptors is a promising strategy to prevent deleterious inflammatory responses that mediate pathogenesis and severity of malaria

Type I Interferon Transcriptional Signature in Neutrophils and Low-Density Granulocytes Are Associated with Tissue Damage in Malaria

Neutrophils are the most abundant leukocyte population in the bloodstream, the primary compartment of Plasmodium sp. infection. However, the role of these polymorphonuclear cells in mediating either the resistance or the pathogenesis of malaria is poorly understood. We report that circulating neutrophils from malaria patients are highly activated, as indicated by a strong type I interferon transcriptional signature, increased expression of surface activation markers, enhanced release of reactive oxygen species and myeloperoxidase, and a high frequency of low-density granulocytes. The activation of neutrophils was associated with increased levels of serum alanine and aspartate aminotransferases, indicating liver damage. In a rodent malaria model, we observed intense recruitment of neutrophils to liver sinusoids. Neutrophil migration and IL-1β and chemokine expression as well as liver damage were all dependent on type I interferon signaling. The data suggest that type I interferon signaling has a central role in neutrophil activation and malaria pathogenesis.status: publishe

Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome

Submitted by Nuzia Santos ([email protected]) on 2015-08-31T18:03:50Z No. of bitstreams: 1 Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome.pdf: 13560839 bytes, checksum: de23e4884d718a23dd2c980651b9a4be (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-08-31T18:03:57Z (GMT) No. of bitstreams: 1 Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome.pdf: 13560839 bytes, checksum: de23e4884d718a23dd2c980651b9a4be (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-08-31T18:10:09Z (GMT) No. of bitstreams: 1 Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome.pdf: 13560839 bytes, checksum: de23e4884d718a23dd2c980651b9a4be (MD5)Made available in DSpace on 2015-08-31T18:10:09Z (GMT). No. of bitstreams: 1 Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome.pdf: 13560839 bytes, checksum: de23e4884d718a23dd2c980651b9a4be (MD5) Previous issue date: 2011University of Massachusetts Medical School. Department of Medicine. Division of Infectious Diseases and Immunology. Worcester, MA, USAUniversity of Massachusetts Medical School. Department of Medicine. Division of Infectious Diseases and Immunology. Worcester, MA, USAUniversity of Massachusetts Medical School. Department of Medicine. Division of Infectious Diseases and Immunology. Worcester, MA, USAUniversity of Massachusetts Medical School. Department of Medicine. Division of Infectious Diseases and Immunology. Worcester, MA, USAUniversity of Massachusetts Medical School. Department of Medicine. Division of Infectious Diseases and Immunology. Worcester, MA, USAUniversity of Massachusetts Medical School. Department of Medicine. Division of Infectious Diseases and Immunology. Worcester, MA, USAUniversity of Massachusetts Medical School. Department of Medicine. Division of Infectious Diseases and Immunology. Worcester, MA, USAUniversidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Parasitologia, Bioquimica e Imunologia. Belo Horizonte, MG, BrasilUniversity of Massachusetts Medical School. Department of Medicine. Division of Infectious Diseases and Immunology. Worcester, MA, USADepartment of Inflammation and Remodeling, Pfizer. Cambridge, MA, USAUniversity of Miami School of Medicine. Department of Medicine. Division of Hematology and Oncology. Miami, FL, USAUniversity of Massachusetts Medical School. Department of Medicine. Division of Infectious Diseases and Immunology. Worcester, MA, USA/Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Parasitologia, Bioquimica e Imunologia. Belo Horizonte, MG, Brasil/Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratorio de Imunopatologia. Belo Horizonte, MG, BrasilUniversity of Massachusetts Medical School. Department of Medicine. Division of Infectious Diseases and Immunology. Worcester, MA, USAUniversity of Massachusetts Medical School. Department of Medicine. Division of Infectious Diseases and Immunology. Worcester, MA, USAAlthough Toll-like receptor 9 (TLR9) has been implicated in regulating cytokine and type I interferon (IFN) production during malaria in humans and mice, the high AT content of the Plasmodium falciparum genome prompted us to examine the possibility that malarial DNA triggered TLR9-independent DNA sensing pathways. Over 6000 ATTTTTAC (“AT-rich”) motifs are present in the genome of P. falciparum, which we show here potently induce type I IFNs. Parasite DNA, parasitized erythrocytes and oligonucleotides containing the AT-r motif induce type I IFNs via a pathway that did not involve previously described sensors including TLR9, DAI, RNA polymerase-III or IFI16/p204. Rather, AT-rich DNA sensing involved an unknown receptor that coupled to STING, TBK1 and IRF3-IRF7 signaling pathway. Mice lacking both IRF3 and IRF7, the kinase TBK1 or the type I IFN receptor were resistant to otherwise lethal cerebral malaria. Collectively, these observations implicate AT-rich DNA sensing via STING, TBK1 and IRF3-IRF7 in P. falciparum malaria

Malaria-Induced NLRP12/NLRP3-Dependent Caspase-1 Activation Mediates Inflammation and Hypersensitivity to Bacterial Superinfection

Submitted by Nuzia Santos ([email protected]) on 2015-01-28T12:09:17Z No. of bitstreams: 1 2014_002.pdf: 2147020 bytes, checksum: 47ef449ba2d2a630f98be822cfdd132a (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-01-28T12:09:24Z (GMT) No. of bitstreams: 1 2014_002.pdf: 2147020 bytes, checksum: 47ef449ba2d2a630f98be822cfdd132a (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-01-28T12:21:41Z (GMT) No. of bitstreams: 1 2014_002.pdf: 2147020 bytes, checksum: 47ef449ba2d2a630f98be822cfdd132a (MD5)Made available in DSpace on 2015-01-28T12:21:41Z (GMT). No. of bitstreams: 1 2014_002.pdf: 2147020 bytes, checksum: 47ef449ba2d2a630f98be822cfdd132a (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil/University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, United States of America.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil/University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, United States of America.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Ribeirão Preto, SP, Brazil.University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, United States of America.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Ribeirão Preto, SP, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil.Centro de Pesquisas em Medicina Tropical. Porto Velho, RO, Brazil.University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, United States of America.University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, United States of America.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil/University of Massachusetts Medical School. Division of Infectious Diseases and Immunology Worcester, MA, United States of America.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil/University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, United States of America.Cyclic paroxysm and high fever are hallmarks of malaria and are associated with high levels of pyrogenic cytokines, including IL-1β. In this report, we describe a signature for the expression of inflammasome-related genes and caspase-1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-γ-priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or NLRP12. Pro-IL-1β expression required a second stimulation with LPS and was also dependent on IFN-γ-priming and functional TNFR1. As a consequence of Plasmodium-induced caspase-1 activation, mice produced extremely high levels of IL-1β upon a second microbial stimulus, and became hypersensitive to septic shock. Therapeutic intervention with IL-1 receptor antagonist prevented bacterial-induced lethality in rodents. Similar to mice, we observed a significantly increased frequency of circulating CD14+CD16−Caspase-1+ and CD14dimCD16+Caspase-1+ monocytes in peripheral blood mononuclear cells from febrile malaria patients. These cells readily produced large amounts of IL-1β after stimulation with LPS. Furthermore, we observed the presence of inflammasome complexes in monocytes from malaria patients containing either NLRP3 or NLRP12 pyroptosomes. We conclude that NLRP12/NLRP3-dependent activation of caspase-1 is likely to be a key event in mediating systemic production of IL-1β and hypersensitivity to secondary bacterial infection during malari

DNA-Containing Immunocomplexes Promote Inflammasome Assembly and Release of Pyrogenic Cytokines by CD14+ CD16+ CD64high CD32low Inflammatory Monocytes from Malaria Patients

Submitted by Nuzia Santos ([email protected]) on 2016-04-05T17:25:39Z No. of bitstreams: 1 DNA-Containing Immunocomplex (...) Monocytes from Malaria Patients.pdf: 4339793 bytes, checksum: 1b4586b816c6971792523290aa455335 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2016-04-05T17:31:16Z (GMT) No. of bitstreams: 1 DNA-Containing Immunocomplex (...) Monocytes from Malaria Patients.pdf: 4339793 bytes, checksum: 1b4586b816c6971792523290aa455335 (MD5)Made available in DSpace on 2016-04-05T17:31:16Z (GMT). No. of bitstreams: 1 DNA-Containing Immunocomplex (...) Monocytes from Malaria Patients.pdf: 4339793 bytes, checksum: 1b4586b816c6971792523290aa455335 (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil.University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA / Centro Internacional de Entrenamiento e Investigaciones Medicas. Cali, Colombia.Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA.Centro de Pesquisa em Medicina Tropical. Porto Velho, RO, Brasil.University of California San Diego. School of Medicine. San Diego, CA, USA.The Feinstein Institute for Medical Research. Center for Autoimmune and Musculoskeletal Diseases. Manhasset, NY, USA.University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA.Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA.Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.High levels of circulating immunocomplexes (ICs) are found in patients with either infectious or sterile inflammation. We report that patients with either Plasmodium falciparum or Plasmodium vivax malaria have increased levels of circulating anti-DNA antibodies and ICs containing parasite DNA. Upon stimulation with malaria-induced ICs, monocytes express an NF-κB transcriptional signature. The main source of IC-induced proinflammatory cytokines (i.e., tumor necrosis factor alpha [TNF-α] and interleukin-1β [IL-1β])in peripheral blood mononuclear cells from acute malaria patients was found to be a CD14+ CD16 (FcγRIIIA)+ CD64 (FcγRI)high CD32 (FcγRIIB)low monocyte subset. Monocytes from convalescent patients were predominantly of the classical phenotype (CD14+ CD16−) that produces high levels of IL-10 and lower levels of TNF-α and IL-1β 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

Neutrophils from <i>P. vivax</i>-infected patients produce high levels of superoxide and display enhanced phagocytic function.

<p>Neutrophils were isolated from <i>P. vivax</i>-infected patients (closed circles; n = 15) or healthy donors (open circles; n = 15), and the frequencies of neutrophils reducing NBT (left panel) as well as cell containing zymosan (right panel) were quantified. Significant differences are indicated with <i>p</i>-values using unpaired t test or Mann-Whitney test when a normality test failed.</p