Loss of Tumor Necrosis Factor Production by Human Monocytes in Falciparum Malaria after Their Maturation in Vitro

Nagao, Takayoshi; Uemura, Haruki; Yanagi, Tetsuo; Oishi, Kazunori; Nagatake, Tsuyoshi; Kanbara, Hiroji

doi:10.4269/ajtmh.1996.55.562

Cited by 9 publications

(7 citation statements)

References 11 publications

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“…The interaction between PfEMP-1 on parasitized RBCs and CD36 on monocytes leads to monocyte activation and monokine production in vitro [25], [26], [27]. Monocyte activation during P. falciparum infection is believed to produce elevated levels of TNF and other monokines implicated in the pathogenesis of malaria [28].…”

Section: Resultsmentioning

confidence: 99%

A Role for Fetal Hemoglobin and Maternal Immune IgG in Infant Resistance to Plasmodium falciparum Malaria

et al. 2011

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BackgroundIn Africa, infant susceptibility to Plasmodium falciparum malaria increases substantially as fetal hemoglobin (HbF) and maternal immune IgG disappear from circulation. During the first few months of life, however, resistance to malaria is evidenced by extremely low parasitemias, the absence of fever, and the almost complete lack of severe disease. This resistance has previously been attributed in part to poor parasite growth in HbF-containing red blood cells (RBCs). A specific role for maternal immune IgG in infant resistance to malaria has been hypothesized but not yet identified.Methods and FindingsWe found that P. falciparum parasites invade and develop normally in fetal (cord blood, CB) RBCs, which contain up to 95% HbF. However, these parasitized CB RBCs are impaired in their binding to human microvascular endothelial cells (MVECs), monocytes, and nonparasitized RBCs – cytoadherence interactions that have been implicated in the development of high parasite densities and the symptoms of malaria. Abnormal display of the parasite's cytoadherence antigen P. falciparum erythrocyte membrane protein-1 (PfEMP-1) on CB RBCs accounts for these findings and is reminiscent of that on HbC and HbS RBCs. IgG purified from the plasma of immune Malian adults almost completely abolishes the adherence of parasitized CB RBCs to MVECs.ConclusionsOur data suggest a model of malaria protection in which HbF and maternal IgG act cooperatively to impair the cytoadherence of parasitized RBCs in the first few months of life. In highly malarious areas of Africa, an infant's contemporaneous expression of HbC or HbS and development of an immune IgG repertoire may effectively reconstitute the waning protective effects of HbF and maternal immune IgG, thereby extending the malaria resistance of infancy into early childhood.

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Section: Resultsmentioning

confidence: 99%

A Role for Fetal Hemoglobin and Maternal Immune IgG in Infant Resistance to Plasmodium falciparum Malaria

et al. 2011

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“…They can also accumulate as malaria pigment-laden cells in the placentas of malaria-infected pregnant women [ 13 – 15 ]. Monocytes phagocytose IgG-opsonised IE via Fcγ receptor-mediated mechanisms [ 16 , 17 ] and secrete both pro-inflammatory and anti-inflammatory cytokines and growth factors in response to parasite ingestion which may aid in both parasite clearance and in limiting inflammation [ 18 , 19 ]. Circulating human monocytes exist as separate subsets which are identified by their expression of CD14 (the co-receptor for Toll-like receptor 4 (TLR4) recognition of bacterial lipopolysaccharide) and CD16 (FcγRIIIa: a receptor for IgG).…”

Section: Introductionmentioning

confidence: 99%

CD14hiCD16+ monocytes phagocytose antibody-opsonised Plasmodium falciparum infected erythrocytes more efficiently than other monocyte subsets, and require CD16 and complement to do so

Zhou

Feng

Beeson

et al. 2015

BMC Med

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BackgroundWith more than 600,000 deaths from malaria, mainly of children under five years old and caused by infection with Plasmodium falciparum, comes an urgent need for an effective anti-malaria vaccine. Limited details on the mechanisms of protective immunity are a barrier to vaccine development. Antibodies play an important role in immunity to malaria and monocytes are key effectors in antibody-mediated protection by phagocytosing antibody-opsonised infected erythrocytes (IE). Eliciting antibodies that enhance phagocytosis of IE is therefore an important potential component of an effective vaccine, requiring robust assays to determine the ability of elicited antibodies to stimulate this in vivo. The mechanisms by which monocytes ingest IE and the nature of the monocytes which do so are unknown.MethodsPurified trophozoite-stage P. falciparum IE were stained with ethidium bromide, opsonised with anti-erythrocyte antibodies and incubated with fresh whole blood. Phagocytosis of IE and TNF production by individual monocyte subsets was measured by flow cytometry. Ingestion of IE was confirmed by imaging flow cytometry.ResultsCD14hiCD16+ monocytes phagocytosed antibody-opsonised IE and produced TNF more efficiently than CD14hiCD16- and CD14loCD16+ monocytes. Blocking experiments showed that Fcγ receptor IIIa (CD16) but not Fcγ receptor IIa (CD32a) or Fcγ receptor I (CD64) was necessary for phagocytosis. CD14hiCD16+ monocytes ingested antibody-opsonised IE when peripheral blood mononuclear cells were reconstituted with autologous serum but not heat-inactivated autologous serum. Antibody-opsonised IE were rapidly opsonised with complement component C3 in serum (t1/2 = 2-3 minutes) and phagocytosis of antibody-opsonised IE was inhibited in a dose-dependent manner by an inhibitor of C3 activation, compstatin. Compared to other monocyte subsets, CD14hiCD16+ monocytes expressed the highest levels of complement receptor 4 (CD11c) and activated complement receptor 3 (CD11b) subunits.ConclusionsWe show a special role for CD14hiCD16+ monocytes in phagocytosing opsonised P. falciparum IE and production of TNF. While ingestion was mediated by Fcγ receptor IIIa, this receptor was not sufficient to allow phagocytosis; despite opsonisation with antibody, phagocytosis of IE also required complement opsonisation. Assays which measure the ability of vaccines to elicit a protective antibody response to P. falciparum should consider their ability to promote phagocytosis and fix complement.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0391-7) contains supplementary material, which is available to authorized users.

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“…Thus, these CAMφ significantly enhanced the phagocytosis, adhesion, proliferation, and anti-schisotosomal abilities via secretion of high levels of reactive oxygen and nitrogen intermediates such as NO, PGE 2 , and proinflammatory cytokines (e.g., IL-1β, IL-12, IL-23, and TNF-α) and pro-inflammatory enzymes inducing inducible nitric oxide synthase and cyclooxygenase-2. On the contrary, upon prolonged exposure to IL-4, IL-13, IL-10, or other Th2-associated factors, this CAMφ also undergoes an alternative and changed to AAMφ, which may be losing some function on the elimination of pathogens (Nagao et al 1996;Ishii et al 2009;de Jong et al 2010) and ultimately leads to their overt involvement in the tissue-destructive fibrotic response (Pearce and MacDonald 2002;Wynn et al 2004). The processes of alternatively activated macrophages were shown as an essential part for both host survival and parasite survival.…”

Section: Discussionmentioning

confidence: 96%

Effects of a recombinant schistosomal-derived anti-inflammatory molecular (rSj16) on the lipopolysaccharide (LPS)-induced activated RAW264.7

Sun

Peng

et al. 2012

Parasitol Res

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Macrophages as a principal component of immune system play an important role in the initiation, modulation, and final activation of immune response against pathogens including schistosomes. Classical (M1) or alternative (M2) activation states of macrophage have different functions during infections. Previously, we report that the schistosomal-derived anti-inflammatory molecule coding gene (named Sj16) was isolated and the recombinant Sj16 (rSj16) was expressed in Escherichia coli. rSj16 has been demonstrated to have definite anti-inflammatory effect in vivo and in vitro on rodent model. To study the molecular basis on anti-inflammatory of rSj16, in the present paper, we investigate the effects of rSj16 on the lipopolysaccharide (LPS)-induced activated RAW264.7, a murine macrophage cell line. We found that rSj16 inhibited LPS-induced activation of RAW264.7, as evidenced by impacting the proliferation, phagocytosis, and migration of the RAW264.7. After pretreated with rSj16, it showed the most potent inhibitory effects of rSj16 on the nitric oxide production in RAW264.7 cells. Furthermore, rSj16 also significantly decreased the levels of proinflammatory cytokines such as PGE2, IL-1β, IL-6, IL-12, IL-23, and TNF-α, whereas it increased the levels of immunosuppressive cytokine IL-10. rSj16 can also inhibit the LPS-induced activation of NF-κβ. These results further imply that Sj16 contributes to the immune evasion of Schistosoma japonicum through alternatively activated macrophage (M2), and rSj16 is expected to serve as a potential drug source for the medication of inflammatory disorders.

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Loss of Tumor Necrosis Factor Production by Human Monocytes in Falciparum Malaria after Their Maturation in Vitro

Cited by 9 publications

References 11 publications

A Role for Fetal Hemoglobin and Maternal Immune IgG in Infant Resistance to Plasmodium falciparum Malaria

A Role for Fetal Hemoglobin and Maternal Immune IgG in Infant Resistance to Plasmodium falciparum Malaria

CD14hiCD16+ monocytes phagocytose antibody-opsonised Plasmodium falciparum infected erythrocytes more efficiently than other monocyte subsets, and require CD16 and complement to do so

Effects of a recombinant schistosomal-derived anti-inflammatory molecular (rSj16) on the lipopolysaccharide (LPS)-induced activated RAW264.7

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