Disease Tolerance: Linking Sickness Behaviours to Metabolism Helps Mitigate Malaria

Vale, Pedro F.

doi:10.1016/j.cub.2018.04.031

Cited by 4 publications

(4 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our understanding of how, in the context of moderate to high exposure to parasite and host components in the bloodstream of malaria-infected subjects, the majority of clinical cases lack overt clinical disease and complications is still limited (Sinton, 1938;Crompton et al, 2014). In addition to evolutionary human adaptation to malaria parasites that confer host resistance (Júnior et al, 2010;Piel et al, 2013;Vale, 2018;Wang et al, 2018), multiple mechanisms have been proposed to explain malaria tolerance. In this study, we observed that IFN-γ and serum kynurenines increase to both control the infection and to avoid host immunopathology.…”

Section: Discussionmentioning

confidence: 99%

A First Plasmodium vivax Natural Infection Induces Increased Activity of the Interferon Gamma-Driven Tryptophan Catabolism Pathway

Santos¹,

Cruz²,

Lopes³

et al. 2020

Front. Microbiol.

View full text Add to dashboard Cite

The human immune response that controls Plasmodium infection in the liver and blood stages of the parasite life cycle is composed by both pro-and anti-inflammatory programs. Pro-inflammatory responses primarily mediated by IFN-γ controls the infection, but also induce tolerogenic mechanisms to limit host damage, including the tryptophan (TRP) catabolism pathway mediated by the enzyme Indoleamine 2,3-Dioxygenase (IDO1), an enzyme that catalyzes the degradation of TRP to kynurenines (KYN). Here we assessed total serum kynurenines and cytokine dynamics in a cohort of natural Plasmodium vivax human infection and compared them to those of endemic healthy controls and other febrile diseases. In acute malaria, the absolute free kynurenine (KYN) serum levels and the KYN to TRP (KYN/TRP) ratio were significantly elevated in patients compared to healthy controls. Individuals with a diagnosis of a first malaria episode had higher serum KYN levels than individuals with a previous malaria episode. We observed an inverse relationship between the serum levels of IFN-γ and IL-10 in patients with a first malaria episode compared to those of subjects with previous history of malaria. Kynurenine elevation was positively correlated with serum IFN-γ levels in acute infection, whereas, it was negatively correlated with parasite load and P. vivax LDH levels. Overall, the differences observed between infected individuals depended on the number of Plasmodium infections. The decrease in the KYN/TRP ratio in malariaexperienced subjects coincided with the onset of anti-P. vivax IgG. These results suggest that P. vivax infection induces a strong anti-inflammatory program in individuals with first time malaria, which fades with ensuing protective immunity after subsequent episodes. Understanding the tolerance mechanisms involved in the initial exposure would help in defining the balance between protective and pathogenic immune responses necessary to control infection and to improve vaccination strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

A First Plasmodium vivax Natural Infection Induces Increased Activity of the Interferon Gamma-Driven Tryptophan Catabolism Pathway

Santos¹,

Cruz²,

Lopes³

et al. 2020

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Regarding the pathogen, virulence is a crucial trait to consider in host shift studies. Virulence is the cost in fitness a pathogen causes to its host due to infection (Read, 1994;Vale et al, 2016Vale et al, , 2018, and it may vary following a host shift, presenting high levels in particular species and leading to outbreaks and epidemics (Woolhouse et al, 2005;Jones et al, 2008). Initially, virulence was thought to be a direct consequence of parasite replication, being linked to the idea that the host-parasite interaction evolves towards avirulence, i.e.…”

Section: Experiments On Host-shiftmentioning

confidence: 99%

Host-shift as the cause of emerging infectious diseases: Experimental approaches using Drosophila-virus interactions

2021

View full text Add to dashboard Cite

Host shifts, when a cross-species transmission of a pathogen can lead to successful infections, are the main cause of emerging infectious diseases, such as COVID-19. A complex challenge faced by the scientific community is to address the factors that determine whether the cross-species transmissions will result in spillover or sustained onwards infections. Here we review recent literature and present a perspective on current approaches we are using to understand the mechanisms underlying host shifts. We highlight the usefulness of the interactions between Drosophila species and viruses as an ideal study model. Additionally, we discuss how cross-infection experiments-when pathogens from a natural reservoir are intentionally injected in novel host species-can test the effect cross-species transmissions may have on the fitness of virus and host, and how the host phylogeny may influence this response. We also discuss experiments evaluating how cooccurrence with other viruses or the presence of the endosymbiont bacteria Wolbachia may affect the performance of new viruses in a novel host. Finally, we discuss the need of surveys of virus diversity in natural populations using next-generation sequencing technologies. In the long term, these approaches can contribute to a better understanding of the basic biology of host shifts.

show abstract

“…In this way, our results indicate that host species may be varying in tolerance during DAV infection. One potential way in which hosts may tolerate infections is via sickness behaviours, such as change in body temperature, reduced eating and drinking, anorexia, lethargy and hypothermia (Arnold et al, 2013;Vale, 2018). A study infecting D.…”

Section: Similarly Three Strains Of Sigma Viruses (Rhabdoviridae) Inmentioning

confidence: 99%

“…Resistance is when there is a mechanism able to avoid or to control pathogen's replication, and tolerance, when there is the activation of a mechanism to avoid a decrease in its own fitness without necessarily altering the parasite load (Medzhitov et al, 2012;Ayres & Schneider, 2012;Vale et al, 2016). Virulence is the cost in fitness a pathogen causes to its host due to infection (Read, 1994;Vale et al, 2016;Vale, 2018), and it may vary following a host shift, presenting high levels in particular species and leading to outbreaks and epidemics (Woolhouse, 2005;Jones et al, 2008). Initially, virulence was thought to be a direct consequence of parasite replication, being linked to the idea that the host-parasite interaction evolves towards avirulence, i.e.…”

Section: Introductionmentioning

confidence: 99%

Variation in host susceptibility to different pathogens: an experimental and phylogenetic study of Drosophila-viruses

Beraldo¹

View full text Add to dashboard Cite

Disease Tolerance: Linking Sickness Behaviours to Metabolism Helps Mitigate Malaria

Cited by 4 publications

References 20 publications

A First Plasmodium vivax Natural Infection Induces Increased Activity of the Interferon Gamma-Driven Tryptophan Catabolism Pathway

A First Plasmodium vivax Natural Infection Induces Increased Activity of the Interferon Gamma-Driven Tryptophan Catabolism Pathway

Host-shift as the cause of emerging infectious diseases: Experimental approaches using Drosophila-virus interactions

Variation in host susceptibility to different pathogens: an experimental and phylogenetic study of Drosophila-viruses

Contact Info

Product

Resources

About