Immunopathology of malaria: role of cytokine production and adhesion molecules

Grau, Georges E.; Piguet, P F; Lambert, Paul‐Henri

doi:10.1590/s0074-02761992000900014

Cited by 4 publications

(2 citation statements)

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“…Because inflammatory cytokines are induced during malaria and contribute to its control, it is possible that the same cytokines could interfere with HBV replication in the liver in coinfected individuals. Indeed, high levels of TNF-␣ , IFN-␥ , and IL-6 are detectable in the blood of malaria patients and in the spleen and liver in rodent models of malaria (11,(27)(28)(29)(30)(31)(32). Furthermore, parasitized RBCs are cleared by resident hepatic and splenic macrophages (33,34) that can not only secrete antiviral cytokines but also function as antigen presenting cells, and produce chemokines that lead to recruitment of T cells that can secrete their own salvo of antiviral cytokines in the infected liver.…”

Section: Introductionmentioning

confidence: 99%

Host–Virus Interactions during Malaria Infection in Hepatitis B Virus Transgenic Mice

Pasquetto

Guidotti

Kakimi

et al. 2000

The Journal of Experimental Medicine

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We have previously shown that hepatitis B virus (HBV) replication is abolished in the liver of HBV transgenic mice by inflammatory cytokines induced by HBV-specific cytotoxic T cells and during unrelated viral infections of the liver. We now report that intrahepatic HBV replication is also inhibited in mice infected by the malaria species Plasmodium yoelii 17X NL. P. yoelii infection triggers an intrahepatic inflammatory response characterized by the influx of natural killer cells, macrophages, and T cells. During this process, interferon (IFN)-γ and IFN-α/β suppress HBV gene expression and replication in the liver. Collectively, the data suggest that malaria infection might influence the course and pathogenesis of HBV infection in coinfected humans.

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Section: Introductionmentioning

confidence: 99%

Host–Virus Interactions during Malaria Infection in Hepatitis B Virus Transgenic Mice

Pasquetto

Guidotti

Kakimi

et al. 2000

The Journal of Experimental Medicine

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“…Extrapolation of results obtained with the mouse model of cerebral malaria must be done with caution because there are many differences between the pathogenesis of P. berghei-infected mice and the pathogenesis of P. falciparum-infected humans. We selected P. berghei-infected mice instead of Plasmodium yoelii-infected mice (a second model of cerebral malaria) because P. berghei-infected mice exhibit (i) a marked inflammatory response, (ii) profound thrombocytopenia, and (iii) obtundation, which P. yoelii-infected mice do not (6,12,13,21). Like P. falciparum-parasitized erythrocytes, both P. yoelii-and P. berghei-parasitized erythrocytes sequester by adhering to brain microvasculature (15,21).…”

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confidence: 99%

Inhibition of Platelet Adherence to Brain Microvasculature Protects against SeverePlasmodium bergheiMalaria

Sun¹,

Chang²,

Li³

et al. 2003

Infect Immun

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Some patients with Plasmodium falciparum infections develop cerebral malaria, acute respiratory distress, and shock and ultimately die even though drug therapy has eliminated the parasite from the blood, suggesting that a systemic inflammatory response contributes to malarial pathogenesis. Plasmodium berghei-infected mice are a well-recognized model of severe malaria (experimental severe malaria [ESM]), and infected mice exhibit a systemic inflammatory response. Because platelets are proposed to contribute to ESM and other systemic inflammatory responses, we determined whether platelet adherence contributes to experimental malarial pathogenesis. Indeed, a significant (P < 0.005) increase in the number of rolling and adherent platelets was observed by intravital microscopy in brain venules of P. berghei-infected mice compared with the number in uninfected controls. P-selectin-or ICAM-1-deficient mice exhibit increased survival after P. berghei infection. We observed a significant (P < 0.0001) reduction in the morbidity of mice injected with anti-CD41 (␣ IIb or gpIIb) monoclonal antibody on day 1 of P. berghei infection compared with the morbidity of infected controls injected with rat immunoglobulin G. Additionally, platelet rolling and adhesion in brain venules were reduced in P. berghei mice lacking either P-selectin or ICAM-1 or when the platelets were coated with anti-CD41 monoclonal antibody. Unlike other inflammatory conditions, we did not detect platelet-leukocyte interactions during P. berghei malaria. Because (i) leukocyte adhesion is not markedly altered in the absence of P-selectin or ICAM-1 and (ii) CD41 is not an adhesion molecule for parasitized erythrocytes, these findings support the hypothesis that inhibition of platelet adhesion to the brain microvasculature protects against development of malarial pathogenesis.

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Is Ischemia Involved in the Pathogenesis of Murine Cerebral Malaria?

Sanni

Rae

Maitland

et al. 2001

The American Journal of Pathology

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Sequestration of parasitized erythrocytes in the central nervous system microcirculation and increased cerebrospinal fluid lactate are prominent features of cerebral malaria (CM), suggesting that sequestration causes mechanical obstruction and ischemia. To examine the potential role of ischemia in the pathogenesis of CM, Plasmodium berghei ANKA (PbA) infection in CBA mice was compared to infection with P. berghei K173 (PbK) which does not cause CM (the non-CM model, NCM). Cerebral metabolite pools were measured by (1)H nuclear magnetic resonance spectroscopy during PbA and PbK infections. Lactate and alanine concentrations increased significantly at the terminal stage of CM, but not in NCM mice at any stage. These changes did not correlate with parasitemia. Brain NAD/NADH ratio was unchanged in CM and NCM mice at any time studied, but the total NAD pool size decreased significantly in the CM mice on day 7 after inoculation. Brain levels of glutamine and several essential amino acids were increased significantly in CM mice. There was a significant linear correlation between the time elapsed after infection and small, progressive decreases in the cell density/cell viability markers glycerophosphocholine and N-acetylaspartate in CM, indicative of gradual loss of cell viability. The metabolite changes followed a different pattern, with a sudden significant alteration in the levels of lactate, alanine, and glutamine at the time of terminal CM. In NCM, there were significant decreases with time of glutamate, the osmolyte myo-inositol, and glycerophosphocholine. These results are consistent with an ischemic change in the metabolic pattern of the brain in CM mice, whereas in NCM mice the changes were more consistent with hypoxia without vascular obstruction. Mild obstructive ischemia is a likely cause of the metabolic changes during CM, but a role for immune cell effector molecules cannot be ruled out.

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Immunopathology of malaria: role of cytokine production and adhesion molecules

Cited by 4 publications

References 0 publications

Host–Virus Interactions during Malaria Infection in Hepatitis B Virus Transgenic Mice

Host–Virus Interactions during Malaria Infection in Hepatitis B Virus Transgenic Mice

Inhibition of Platelet Adherence to Brain Microvasculature Protects against SeverePlasmodium bergheiMalaria

Is Ischemia Involved in the Pathogenesis of Murine Cerebral Malaria?

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