Malaria circumsporozoite protein inhibits the respiratory burst in Kupffer cells

Usynin, I. F.; Klotz, Christian; Frevert, Ute

doi:10.1111/j.1462-5822.2007.00982.x

Cited by 86 publications

(71 citation statements)

References 151 publications

(185 reference statements)

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“…The role of cAMP in augmenting infection has been shown by others (48), and our study adds further evidence to this notion. The effects of cAMP are mediated by two ubiquitously expressed [cAMP] i receptors: the classical PKA and the recently discovered EPAC (49). Significant reduction in parasite number in the presence of PKA inhibitor suggested greater contribution of PKA in mediating downstream effects of cAMP.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 Negatively Regulates the Production of Inflammatory Cytokines/Chemokines and IL-17 in Visceral Leishmaniasis

Saha

Biswas

Srivastav

et al. 2014

The Journal of Immunology

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Persistence of intracellular infection depends on the exploitation of factors that negatively regulate the host immune response. In this study, we elucidated the role of macrophage PGE2, an immunoregulatory lipid, in successful survival of Leishmania donovani, causative agent of the fatal visceral leishmaniasis. PGE2 production was induced during infection and resulted in increased cAMP level in peritoneal macrophages through G protein–coupled E-series prostanoid (EP) receptors. Among four different EPs (EP1–4), infection upregulated the expression of only EP2, and individual administration of either EP2-specific agonist, butaprost, or 8-Br–cAMP, a cell-permeable cAMP analog, promoted parasite survival. Inhibition of cAMP also induced generation of reactive oxygen species, an antileishmanial effector molecule. Negative modulation of PGE2 signaling reduced infection-induced anti-inflammatory cytokine polarization and enhanced inflammatory chemokines, CCL3 and CCL5. Effect of PGE2 on cytokine and chemokine production was found to be differentially modulated by cAMP-dependent protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC). PGE2-induced decreases in TNF-α and CCL5 were mediated specifically by PKA, whereas administration of brefeldin A, an EPAC inhibitor, could reverse decreased production of CCL3. Apart from modulating inflammatory/anti-inflammatory balance, PGE2 inhibited antileishmanial IL-17 cytokine production in splenocyte culture. Augmented PGE2 production was also found in splenocytes of infected mice, and administration of EP2 antagonist in mice resulted in reduced liver and spleen parasite burden along with host-favorable T cell response. These results suggest that Leishmania facilitates an immunosuppressive environment in macrophages by PGE2-driven, EP2-mediated cAMP signaling that is differentially regulated by PKA and EPAC.

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Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 Negatively Regulates the Production of Inflammatory Cytokines/Chemokines and IL-17 in Visceral Leishmaniasis

Saha

Biswas

Srivastav

et al. 2014

The Journal of Immunology

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“…This would be a prime target for vaccination. How the sporozoite escapes triggering the respiratory burst is not completely understood, but involves CSP binding (Usynin et al 2007); thus, antibodies bound to CSP may act to reverse this respiratory burst inhibition or provide an opsonization signal for phagocytic activity by Kupffer cells.…”

Section: Approaches To Development Of Vimtmentioning

confidence: 99%

Vaccines to Accelerate Malaria Elimination and Eventual Eradication

Healer

Cowman

Kaslow³

et al. 2017

Cold Spring Harb Perspect Med

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Remarkable progress has been made in coordinated malaria control efforts with substantial reductions in malaria-associated deaths and morbidity achieved through mass administration of drugs and vector control measures including distribution of long-lasting insecticideimpregnated bednets and indoor residual spraying. However, emerging resistance poses a significant threat to the sustainability of these interventions. In this light, the malaria research community has been charged with the development of a highly efficacious vaccine to complement existing malaria elimination measures. As the past 40 years of investment in this goal attests, this is no small feat. The malaria parasite is a highly complex organism, exquisitely adapted for survival under hostile conditions within human and mosquito hosts. Here we review current vaccine strategies to accelerate elimination and the potential for novel and innovative approaches to vaccine design through a better understanding of the host-parasite interaction.

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“…Both sporozoites and liver stages have evolved a plethora of strategies to antagonize the host responses. A role for CSP in preventing the activation of respiratory burst while migrating through the liver resident Kupffer cells was reported (Usynin et al, 2007). In this regard, both CSP and sporozoites are capable of inducing the Science Publications AJI cAMP production in Kupffer cells that have the ability to inhibit the NADPH oxidase activity necessary for generation of reactive oxygen species.…”

Section: Overcoming the Host Defence Responsesmentioning

confidence: 99%

<i>PLASMODIUM</i> PRE-ERYTHROCYTIC STAGES: BIOLOGY, WHOLE PARASITE VACCINES AND TRANSGENIC MODELS

Kumar

Mishra

2012

American Journal of Immunology

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Malaria remains one of the world's worst health problems, which causes 216 million new cases and approximately 655,000 deaths every year WHO World Malaria Report, 2011. Malaria transmission to the mammalian host is initiated through a mosquito bite that delivers sporozoites into the vertebrate host. The injected sporozoites are selectively targeted to liver which is the first obligatory step in infection thus making this stage an attractive target for both drug and vaccine development. Research using rodent models of malaria has greatly facilitated the understanding of several aspects of pre-erythrocytic parasite biology and immunology. However, translation of this knowledge to combat Plasmodium falciparum infections still offers several challenges. We highlight in this review some of the recent advances in the field of Plasmodium sporozoite and liver stage biology and in the generation of whole organism attenuated vaccines. We also comment on the application of transgenic models central to Circumsporozoite Protein (CSP) in understanding the mechanism of pre-erythrocytic immunity.

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Malaria circumsporozoite protein inhibits the respiratory burst in Kupffer cells

Cited by 86 publications

References 151 publications

Prostaglandin E2 Negatively Regulates the Production of Inflammatory Cytokines/Chemokines and IL-17 in Visceral Leishmaniasis

Prostaglandin E2 Negatively Regulates the Production of Inflammatory Cytokines/Chemokines and IL-17 in Visceral Leishmaniasis

Vaccines to Accelerate Malaria Elimination and Eventual Eradication

<i>PLASMODIUM</i> PRE-ERYTHROCYTIC STAGES: BIOLOGY, WHOLE PARASITE VACCINES AND TRANSGENIC MODELS

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