Non specific resistance against malaria pre-erythrocytic stages: involvement of acute phase proteins

Pied, Sylviane; Tabone, Marie‐Dominique; Châtellier, Gilles; Marussig, Myriam; Jardel, Claude; Nosten, François; Mazier, Dominique

doi:10.1051/parasite/1995023263

Cited by 12 publications

(5 citation statements)

References 9 publications

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“…Alteration of the levels of several acute phase proteins (APPs) and multiple members of serum complement cascade as well as complement regulatory proteins ( Table 2) due to the plasmodial infections is consistent with earlier findings [19][20][21]. Increased expression levels of circulating acute-phase amyloid proteins like serum amyloid A and P provide non-specific resistance against the pre-erythrocytic stages of Plasmodium, limit tissue damage and promote a rapid return to homeostasis [22,23]. Interestingly, human serum paraoxonase (PON1) an HDLassociated esterase which protects lipoproteins against oxidation, found to be down-regulated in falciparum malaria patients.…”

Section: Discussionsupporting

confidence: 88%

Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers

Renu

Srivastava

et al. 2012

PLoS ONE

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This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.

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Section: Discussionsupporting

confidence: 88%

Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers

Renu

Srivastava

et al. 2012

PLoS ONE

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“…This suggest strongly that this acute phase protein does not mediate the TNF-α effect. It has been reported previously that two other acute phase proteins, the protease inhibitors α1-antitrypsin and α2 macroglobulin, were also able to prevent sporozoite infection and development [42]. Parasite proteases are necessary for sporozoite invasion in hepatocytes [43] and thus may be targeted by these two protease inhibitors.…”

Section: Discussionmentioning

confidence: 98%

Inhibitory Effect of TNF-α on Malaria Pre-Erythrocytic Stage Development: Influence of Host Hepatocyte/Parasite Combinations

et al. 2011

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BackgroundThe liver stages of malaria parasites are inhibited by cytokines such as interferon-γ or Interleukin (IL)-6. Binding of these cytokines to their receptors at the surface of the infected hepatocytes leads to the production of nitric oxide (NO) and radical oxygen intermediates (ROI), which kill hepatic parasites. However, conflicting results were obtained with TNF-α possibly because of differences in the models used. We have reassessed the role of TNF-α in the different cellular systems used to study the Plasmodium pre-erythrocytic stages.Methods and FindingsHuman or mouse TNF-α were tested against human and rodent malaria parasites grown in vitro in human or rodent primary hepatocytes, or in hepatoma cell lines. Our data demonstrated that TNF-α treatment prevents the development of malaria pre-erythrocytic stages. This inhibitory effect however varies with the infecting parasite species and with the nature and origin of the cytokine and hepatocytes. Inhibition was only observed for all parasite species tested when hepatocytes were pre-incubated 24 or 48 hrs before infection and activity was directed only against early hepatic parasite. We further showed that TNF-α inhibition was mediated by a soluble factor present in the supernatant of TNF-α stimulated hepatocytes but it was not related to NO or ROI. Treatment TNF-α prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified.ConclusionsTreatment TNF-α prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. However, the nature of the cytokine-host cell-parasite combination must be carefully considered for extrapolation to the human infection.

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“…by a CTL effect) or indirectly either by their mediators or T-cell driven recruitment of inflammatory cells, predominantly polymorphs macrophages and Kuppfer cells. Among the many immune mediators in which a protective effect was reported, the most potent are interleukin 12 (IL12) [33], interferon gamma (IFN-γ) [20,34-36], O 2 - [37], and NO radicals, but also, NO synthase [38-40], TNF [41,42], IL1 [35], IL6 [43] leading to the secretion of C-reactive protein [44], hemopexin, α1-anti-trypsin and α2-macroglobulin to name but a few, whose ability to block liver schizogony was reported as being highly effective [45]. …”

Section: Introductionmentioning

confidence: 99%

Interferon-γ, a valuable surrogate marker of Plasmodium falciparum pre-erythrocytic stages protective immunity

Perlaza

Sauzet

Brahimi

et al. 2011

Malar J

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Immunity against the pre-erythrocytic stages of malaria is the most promising, as it is strong and fully sterilizing. Yet, the underlying immune effectors against the human Plasmodium falciparum pre-erythrocytic stages remain surprisingly poorly known and have been little explored, which in turn prevents any rational vaccine progress. Evidence that has been gathered in vitro and in vivo, in higher primates and in humans, is reviewed here, emphasizing the significant role of IFN-γ, either as a critical immune mediator or at least as a valuable surrogate marker of protection. One may hope that these results will trigger investigations in volunteers immunized either by optimally irradiated or over-irradiated sporozoites, to quickly delineate better surrogates of protection, which are essential for the development of a successful malaria vaccine.

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Non specific resistance against malaria pre-erythrocytic stages: involvement of acute phase proteins

Cited by 12 publications

References 9 publications

Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers

Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers

Inhibitory Effect of TNF-α on Malaria Pre-Erythrocytic Stage Development: Influence of Host Hepatocyte/Parasite Combinations

Interferon-γ, a valuable surrogate marker of Plasmodium falciparum pre-erythrocytic stages protective immunity

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