Immunomodulation in Plasmodium falciparum malaria: experiments in nature and their conflicting implications for potential therapeutic agents

Abstract

Effective Plasmodium falciparum immunity requires a precisely timed and balanced response of inflammatory and anti-inflammatory immune regulators. These responses begin with innate immune effectors and are modulated over the course of an infection and between episodes to limit inflammation. To date, there are no effective immunomodulatory therapies for severe malaria. Some of the most potent immunomodulators are naturally occurring infections, including helminthic and chronic viral infections. This review examines malaria coinfection with these organisms, and their impact on malaria morbidity and immune responses. Overall, there is compelling evidence to suggest that chronic coinfections can modulate deleterious malaria-specific immune responses, suggesting that therapeutic agents may be effective if utilized early in infection. Examination of the mechanisms of these effects may serve as a platform to identify more targeted and effective malaria immunomodulatory therapeutics.

Keywords::

• coinfection
• helminth
• hepatitis
• HIV
• immunomodulation
• malaria
• Plasmodium falciparum

Financial & competing interests disclosure

This work was supported in part by a grant awarded to CC John from the National Institute of Neurological Disorders and Stroke and the Fogarty International Center (R01 NS055349). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.