Understanding the role of inflammatory cytokines in malaria and related diseases

Clark, Ian A.; Alleva, Lisa M.; Budd, Alison; Cowden, W. B.

doi:10.1016/j.tmaid.2007.07.002

Cited by 91 publications

(95 citation statements)

References 164 publications

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“…These cytokines are necessary for several antiparasitic effector processes, such as skewing the T‐cell response to a more pronounced T helper type 1 (Th1) response during infection,89, 90 directly killing or inhibiting parasite growth, as has been observed for TNF‐ α and IFN‐ γ, 91 and indirectly killing parasites by activating phagocytic cells 85, 91. However, if left unregulated, high levels of these cytokines, and other proinflammatory mediators have detrimental effects57 which manifest as fever and other symptoms of mild and severe malaria 92. Clearly, inflammation is at the core of the pathophysiology of malaria, and an effective control of inflammation 93 may preclude severe disease and, perhaps, the mild clinical manifestations of malaria.…”

Section: The Role Of Inflammation In Malarial Pathogenesismentioning

confidence: 99%

Evaluating antidisease immunity to malaria and implications for vaccine design

Ademolue

Awandare

2017

Immunology

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SummaryImmunity to malaria could be categorized broadly as antiparasite or antidisease immunity. While most vaccine research efforts have focused on antiparasite immunity, the evidence from endemic populations suggest that antidisease immunity is an important component of natural immunity to malaria. The processes that mediate antidisease immunity have, however, attracted little to no attention, and most interests have been directed towards the antibody responses. This review evaluates the evidence for antidisease immunity in endemic areas and discusses the possible mechanisms responsible for it. Given the key role that inflammation plays in the pathogenesis of malaria, regulation of the inflammatory response appears to be a major mechanism for antidisease immunity in naturally exposed individuals.

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Section: The Role Of Inflammation In Malarial Pathogenesismentioning

confidence: 99%

Evaluating antidisease immunity to malaria and implications for vaccine design

Ademolue

Awandare

2017

Immunology

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“…The disease can range from a mild, uncomplicated febrile illness to severe, life-threatening syndromes, including cerebral malaria and severe malarial anemia (41). Studies with human subjects show that severe malaria often resembles a sepsis-like syndrome, in that the excessive production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-␣), interleukin-1 (IL-1), IL-6, and gamma interferon (IFN-␥) can contribute to pathology (19,20,34). A fine balance in the regulation of the inflammatory response by modulatory anti-inflammatory cytokines such as IL-10 and transforming growth factor ␤ (TGF-␤) is required to control parasite replication while limiting immunopathology (25,46).…”

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confidence: 99%

Elevated Levels of thePlasmodium yoeliiHomologue of Macrophage Migration Inhibitory Factor Attenuate Blood-Stage Malaria

et al. 2010

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The excessive production of proinflammatory cytokines plays a significant role in the pathogenesis of severe malaria. Mammalian macrophage migration inhibitory factor (MIF) (mMIF) is an immune mediator that promotes a sustained proinflammatory response by inhibiting the glucocorticoid-mediated downregulation of inflammation. In addition, Plasmodium parasites also encode a homologue of mammalian MIF that is expressed in asexual-stage parasites. We used the Plasmodium yoelii murine model to study the potential role of parasite-encoded MIF in the pathogenesis of malaria. Antibodies raised against purified, non-epitope-tagged P. yoelii MIF (PyMIF) were used to localize expression in trophozoite-and schizont-stage parasites and demonstrate extracellular release. In vitro, recombinant PyMIF was shown to actively induce the chemotaxis of macrophages but did not induce or enhance tumor necrosis factor alpha (TNF-␣) production from peritoneal macrophages. To examine the role of parasite-derived PyMIF in vivo, two transgenic parasite lines that constitutively overexpress PyMIF were generated, one in a nonlethal P. yoelii 17X background [Py17X-MIF(؉)] and the other in a lethal P. yoelii 17XL background [Py17XL-MIF(؉)]. Challenge studies with transgenic parasites in mice showed that the increased expression of PyMIF resulted in a reduction in disease severity. Mice infected with Py17X-MIF(؉) developed lower peak parasitemia levels than controls, while malariaassociated anemia was unaltered. Infection with Py17XL-MIF(؉) resulted in a prolonged course of infection and a reduction in the overall mortality rate. Combined, the data indicate that parasite-derived MIF does not contribute significantly to immunopathology but, through its chemotactic ability toward macrophages, may attenuate disease and prolong infection of highly virulent parasite isolates.

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“…This causes widespread upregulation of multiple cytokines and chemokines that reflects contributions from both the host and the pathogen to an inappropriate inflammatory response (40,59,64). This kind of unbridled host response to a pathogen is now broadly accepted as the cause of host death in infectious diseases like malaria, influenza, and sepsis (6). In light of the absence of any known endo-or exotoxin activity of any virulence factor of Francisella, this hyperimmune response seems to be the cause of the mortality associated with respiratory tularemia (54).…”

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confidence: 99%

Vaccination with an Attenuated Strain of Francisella novicida Prevents T-Cell Depletion and Protects Mice Infected with the Wild-Type Strain from Severe Sepsis

Sharma

Mishra

et al. 2009

Infect Immun

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Francisella tularensis is the causative agent of zoonotic tularemia, a severe pneumonia in humans, and Francisella novicida causes a similarly severe tularemia in mice upon inhalation. The correlates of protective immunity, as well as the virulence mechanisms of this deadly pathogen, are not well understood. In the present study, we compared the host immune responses of lethally infected and vaccinated mice to highlight the host determinants of protection from this disease. Intranasal infection with an attenuated mutant (Mut) of F. novicida lacking a 58-kDa hypothetical protein protected C57BL/6 mice from a subsequent challenge with the fully virulent wild-type strain U112 via the same route. The protection conferred by Mut vaccination was associated with reduced bacterial burdens in systemic organs, as well as the absence of bacteremia. Also, there was reduced lung pathology and associated cell death in the lungs of vaccinated mice. Both vaccinated and nonvaccinated mice displayed an initial 2-day delay in upregulation of signature inflammatory mediators after challenge. Whereas the nonvaccinated mice developed severe sepsis characterized by hypercytokinemia and T-cell depletion, the vaccinated mice displayed moderated cytokine induction and contained increased numbers of ␣␤ T cells. The recall response in vaccinated mice consisted of a characteristic Th1-type response in terms of cytokines, as well as antibody isotypes. Our results show that a regulated Th1 type of cell-mediated and humoral immunity in the absence of severe sepsis is associated with protection from respiratory tularemia, whereas a deregulated host response leading to severe sepsis contributes to mortality.

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Understanding the role of inflammatory cytokines in malaria and related diseases

Cited by 91 publications

References 164 publications

Evaluating antidisease immunity to malaria and implications for vaccine design

Evaluating antidisease immunity to malaria and implications for vaccine design

Elevated Levels of thePlasmodium yoeliiHomologue of Macrophage Migration Inhibitory Factor Attenuate Blood-Stage Malaria

Vaccination with an Attenuated Strain of Francisella novicida Prevents T-Cell Depletion and Protects Mice Infected with the Wild-Type Strain from Severe Sepsis

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