Concurrent infections of cells by two pathogens can enable a reactivation of the first pathogen and the second pathogen's accelerated T-cell exhaustion

Roe, Kevin

doi:10.1016/j.heliyon.2022.e11371

Cited by 3 publications

(6 citation statements)

References 55 publications

(159 reference statements)

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“…A first pathogen could assist a second pathogen with potentially severe outcomes by accelerating T-cell exhaustion of T-cell defenses that would normally target a second pathogen infection [41,42]. Accelerated T-cell exhaustion with insufficient T-cell responses against the second pathogen could enable a first time infection by the second pathogen to replicate extensively and dangerously in a host.…”

Section: Extracellular Effects Of Intracellular Double Pathogen Inter...mentioning

confidence: 99%

“…Several T-cell miRNAs and lncRNAs control CD8 + T-cell survival and development genes, and CD8 + T-cell exhaustion is linked to a number of CD8 + T-cell miRNAs (e.g., miR-15, miR-17, miR-28, miR-29, miR-142, miR-150, miR155, miR198) and lncRNAs (e.g., lncRNA lnc-Tim3, lncRNAcd244) [51,53]. [41,54]. Direct and indirect pathways exist for double pathogen infections to initiate T-cell exhaustion [53][54][55][56][57].…”

Section: T-cell Regulatory Rna Usage and Cd8 + T-cell Exhaustionmentioning

confidence: 99%

“…This could involve inducing T-cell expressions of numerous inhibitory receptors, such as PD-1, and by inducing infected host cell expressions of inhibitory ligands, such as PD-L1, for binding to the inhibitory receptors on the T-cells. A second distinct pathogen infection, such as a virulent pathogen that creates large antigen titers, can benefit from the proexhaustion cytokines, and/or expression of host cell inhibitory ligands by the same infected cell, and accelerate a T-cell exhaustion for the second pathogen [41,42].…”

Section: Accelerated T-cell Exhaustion-severe Outcomes For Second Pat...mentioning

confidence: 99%

“…If the first pathogen creates a latent infection, T-cell exhaustion regarding the first pathogen can assist the first pathogen's reactivation [7,38]. Such reactivations can potentially cause very severe symptoms, e.g., encephalitis, hepatitis or myocarditis, in the case of reactivated protozoan parasites, such as T. gondii, regardless of whether the second pathogen infection completely ends [41,71].…”

Section: Accelerated T-cell Exhaustion Contribution To the Initiation...mentioning

confidence: 99%

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Pathogen regulatory RNA usage enables chronic infections, T-cell exhaustion and accelerated T-cell exhaustion

Roe¹

2023

Mol Cell Biochem

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Pathogens evade or disable cellular immune defenses using regulatory ribonucleic acids (RNAs), including microRNAs and long non-coding RNAs. Pathogenic usage of regulatory RNA enables chronic infections. Chronic infections, using host regulatory RNAs and/or creating pathogenic regulatory RNAs against cellular defenses, can cause T-cell exhaustion and latent pathogen reactivations. Concurrent pathogen infections of cells enable several possibilities. A first pathogen can cause an accelerated T-cell exhaustion for a second pathogen cellular infection. Accelerated T-cell exhaustion for the second pathogen weakens T-cell targeting of the second pathogen and enables a first-time infection by the second pathogen to replicate quickly and extensively. This can induce a large antibody population, which may be inadequately targeted against the second pathogen. Accelerated T-cell exhaustion can explain the relatively short median and average times from diagnosis to mortality in some viral epidemics, e.g., COVID-19, where the second pathogen can lethally overwhelm individuals' immune defenses. Alternatively, if an individual survives, the second pathogen could induce a very high titer of antigen–antibody immune complexes. If the antigen–antibody immune complex titer quickly becomes very high, it can exceed the immune system's phagocytic capability in immuno-deficient individuals, resulting in a Type III hypersensitivity immune reaction. Accelerated T-cell exhaustion in immuno-deficient individuals can be a fundamental cause of several hyperinflammatory diseases and autoimmune diseases. This would be possible when impaired follicular helper CD4 + T-cell assistance to germinal center B-cell somatic hypermutation, affinity maturation and isotype switching of antibodies results in high titers of inadequate antibodies, and this initiates a Type III hypersensitivity immune reaction with proteinase releases which express or expose autoantigens.

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Section: Extracellular Effects Of Intracellular Double Pathogen Inter...mentioning

confidence: 99%

Section: T-cell Regulatory Rna Usage and Cd8 + T-cell Exhaustionmentioning

confidence: 99%

Section: Accelerated T-cell Exhaustion-severe Outcomes For Second Pat...mentioning

confidence: 99%

Section: Accelerated T-cell Exhaustion Contribution To the Initiation...mentioning

confidence: 99%

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Pathogen regulatory RNA usage enables chronic infections, T-cell exhaustion and accelerated T-cell exhaustion

Roe¹

2023

Mol Cell Biochem

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“…The concept of reactivation of the initial pathogen through concurrent infections is supported by various studies. When multiple intracellular pathogens infect the same host cell, they can disable cellular immune defenses and evade immune responses, leading to the reactivation of a latent first pathogen and accelerated T-cell exhaustion or suppression regarding a second pathogen (86)(87)(88)(89). While there is no confirmed evidence indicating genuine latency of EBOV, the existence of concurrent infections may potentially foster an environment that hinders the immune system's capacity to manage the persistence of pathogens, including EBOV (87,(90)(91)(92).…”

Section: Ebov Versus Host Immune System 131 Waned Immunity Of Survivo...mentioning

confidence: 99%

Beyond survival: unraveling the dynamics of Ebola virus resurgence in Sub-Saharan Africa and the remarkable journey of survivors

Asare Fenteng,

Ossei,

Ayibor

et al. 2023

Front. Virol.

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Ebola virus disease (EVD) remains a significant public health threat, with sporadic outbreaks occurring in Sub-Saharan Africa. Survivors of EVD may experience various post-infection symptoms, collectively known as post-Ebola virus syndrome (PES), which include chronic arthralgia, uveitis, headache, and psychosocial stressors. In this review, we discuss the persistence of Ebola virus in survivors and its possible role in the reemergence of current outbreaks. We highlight that waning immunity of survivors enhances viral persistence and may lead to viral reactivation and recurrence of disease in previously affected tissues. The delicate equilibrium between diminished immune cell surveillance and limited viral replication may lead to enduring chronic inflammation. Our systematic review, based on an extensive survivor cohort, underscores the importance of continued research and preparedness efforts to combat future outbreaks through adequate surveillance and timely public health interventions. This review serves as a comprehensive guide to understanding the complexities of EVD survivorship, the challenges of PES, and the strategies to mitigate its impact.

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Toxoplasma-induced behavior changes - is microbial dysbiosis the missing link?

Prandovszky,

Severance,

Splan

et al. 2024

Front. Cell. Infect. Microbiol.

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Toxoplasma gondii (T. gondii) is one of the most successful intracellular protozoa in that it can infect the majority of mammalian cell types during the acute phase of infection. Furthermore, it is able to establish a chronic infection for the host’s entire lifespan by developing an encysted parasite form, primarily in the muscles and brain of the host, to avoid the host immune system. The infection affects one third of the world population and poses an increased risk for people with a suppressed immune system. Despite the dormant characteristics of chronic T. gondii infection, there is much evidence suggesting that this infection leads to specific behavior changes in both humans and rodents. Although numerous hypotheses have been put forth, the exact mechanisms underlying these behavior changes have yet to be understood. In recent years, several studies revealed a strong connection between the gut microbiome and the different organ systems that are affected in T. gondii infection. While it is widely studied and accepted that acute T. gondii infection can lead to a dramatic disruption of the host’s normal, well-balanced microbial ecosystem (microbial dysbiosis), changes in the gut microbiome during the chronic stage of infection has not been well characterized. This review is intended to briefly inspect the different hypotheses that attempt to explain the behavior changes during T. gondii infection. Furthermore, this review proposes to consider the potential link between gut microbial dysbiosis, and behavior changes in T. gondii infection as a novel way to describe the underlying mechanism.

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Concurrent infections of cells by two pathogens can enable a reactivation of the first pathogen and the second pathogen's accelerated T-cell exhaustion

Cited by 3 publications

References 55 publications

Pathogen regulatory RNA usage enables chronic infections, T-cell exhaustion and accelerated T-cell exhaustion

Pathogen regulatory RNA usage enables chronic infections, T-cell exhaustion and accelerated T-cell exhaustion

Beyond survival: unraveling the dynamics of Ebola virus resurgence in Sub-Saharan Africa and the remarkable journey of survivors

Toxoplasma-induced behavior changes - is microbial dysbiosis the missing link?

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