Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response

Reese, Tiffany A.; Bi, Kevin; Kambal, Amal; Filali‐Mouhim, Ali; Beura, Lalit K.; Bürger, Matheus Carvalho; Pulendran, Bali; Sékaly, Rafick Pierre; Jameson, Stephen C.; Masopust, David; Haining, W. Nicholas; Virgin, Herbert W.

doi:10.1016/j.chom.2016.04.003

Cited by 186 publications

(188 citation statements)

References 46 publications

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“…However, many of these infections contribute to the shape of the normal immune system. For example, laboratory mice have less mature immune systems than mice experimentally infected with multiple pathogens or co-housed with so-called “dirty” or pet store mice 1–3 . The balance of persisting infections, immunity, and clinical disease is dependent on the ongoing interplay between host immune responses and the pathogen.…”

Section: Viral Infections and The T Cell Responsementioning

confidence: 99%

CD4+ T Cell Differentiation in Chronic Viral Infections: The Tfh Perspective

Vella

Herati

Wherry

2017

Trends in Molecular Medicine

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CD4+ T cells play a critical role in the response to chronic viral infections during the acute phase and in the partial containment of infections once chronic infection is established. As infection persists, the virus-specific CD4+ T cell response begins to shift in phenotype. The predominant change described in both mouse and human studies of chronic viral infection is a decrease in detectable Th1 responses. Some Th1 loss is due to decreased proliferative potential and decreased cytokine production in the setting of chronic antigen exposure. However, recent data suggest that Th1 dysfunction is accompanied by a shift in the differentiation pathway of virus-specific CD4+ T cells, with enrichment for cells with a T follicular helper cell (Tfh) phenotype. A Tfh-like program during chronic infection has now been identified in virus-specific CD8+ T cells as well. In this review, we discuss what is known about CD4+ T cell differentiation in chronic viral infections, with a focus on the emergence of the Tfh program and the implications of this shift with respect to Tfh function and the host-pathogen interaction.

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Section: Viral Infections and The T Cell Responsementioning

confidence: 99%

CD4+ T Cell Differentiation in Chronic Viral Infections: The Tfh Perspective

Vella

Herati

Wherry

2017

Trends in Molecular Medicine

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“…Indeed, studies in mouse models of MCMV and MHV68 have shown unique alterations in host gene transcription based on single-vs. double-herpesvirus infection (White et al 2010). Furthermore, studies in mice show more Bhuman like^responses to vaccination following sequential infection with common pathogens, including MCMV and MHV68, suggesting that animal models may be improved by exposing them to pathogens commonly encountered in humans, including those which (e.g., CMV) may contribute to the immune phenotype (Reese et al 2016). (3) The reciprocal effect of secondary infections on the immune response to CMVand how this shapes the anti-CMV response over time.…”

Section: Chronic Co-infectionmentioning

confidence: 99%

A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness

Souquette¹,

Frere²,

Smithey³

et al. 2017

GeroScience

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Approximately 50% of individuals aged 6-49 years in the United States are infected with cytomegalovirus (CMV), with seroprevalence increasing with age, reaching 85-90% by 75-80 years according to Bate et al. (Clin Infect Dis 50 (11): 1439-1447 and Pawelec et al. (Curr Opin Immunol 24:507-511, 2012). Following primary infection, CMV establishes lifelong latency with periodic reactivation. Immunocompetent hosts experience largely asymptomatic infection, but CMV can cause serious illness in immunocompromised populations, such as transplant patients and the elderly. Control of CMV requires constant immune surveillance, and recent discoveries suggest this demand alters general features of the immune system in infected individuals. Here, we review recent advances in the understanding of the immune response to CMV and the role of CMV in immune aging and fitness, while highlighting the importance of potential confounding factors that influence CMV studies. Understanding how CMV contributes to shaping Bbaseline^immunity has important implications for a host's ability to mount effective responses to diverse infections and vaccination.

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“…Beside contributing to the vaccine development process, computational approaches open the way to investigate the influence of additional parameters in the responsiveness to vaccines, such as environmental and lifestyle factors, pre-existing immune status, chronic infections, metabolism and geographic localization or other non-canonical factors (Mannick et al, 2014;Pulendran, 2014;Reese et al, 2016). For instance, preexisting immunity, sex, or age related factors were shown to affect the response to hepatitis B and the influenza vaccine (Furman et al, 2014;Fourati et al, 2016).…”

Section: The Making Of a Vaccinementioning

confidence: 99%

Big Data: Challenge and Opportunity for Translational and Industrial Research in Healthcare

Rossi

Grifantini

2018

Front. Digit. Humanit.

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Research and innovation are constant imperatives for the healthcare sector: medicine, biology and biotechnology support it, and more recently computational and data-driven disciplines gained relevance to handle the massive amount of data this sector is and will be generating. To be effective in translational and healthcare industrial research, big data in the life science domain need to be organized, well annotated, catalogued, correlated and integrated: the biggest the data silos at hand, the stronger the need for organization and tidiness. The degree of such organization marks the transition from data to knowledge for strategic decision making. Medicine is supported by observations and data and for certain aspects medicine is becoming a data science supported by clinicians. While medicine defines itself as personalized, quantified (precision med) or in high-definition, clinicians should be prepared to deal with a world in which Internet of People paraphrases the Internet of Things paradigm. Integrated use of electronic health records (EHRs) and quantitative data (both clinical and molecular) is a key process to develop precision medicine. Health records collection was originally designed for patient care and billing and/or insurance purposes. The digitization of health records facilitates and opens up new possibilities for science and research and they should be now collected and managed with this aim in mind. More data and the ability to efficiently handle them is a significant advantage not only for clinicians and life science researchers, but for drugs producers too. In an industrial sector spending increasing efforts on drug repurposing, attention to efficient methods to unwind the intricacies of the hugely complex reality of human physiology, such as network based methods and physical chemistry computational methods, became of paramount importance. Finally, the main pillars of industrial R&D processes for vaccines, include initial discovery, early-late pre clinics, pre-industrialization, clinical phases and finally registration-commercialization. The passage from one step to another is regulated by stringent pass/fail criteria. Bottlenecks of the R&D process are often represented by animal and human studies, which could be rationalized by surrogate in vitro assays as well as by predictive molecular and cellular signatures and models.

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Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response

Cited by 186 publications

References 46 publications

CD4+ T Cell Differentiation in Chronic Viral Infections: The Tfh Perspective

CD4+ T Cell Differentiation in Chronic Viral Infections: The Tfh Perspective

A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness

Big Data: Challenge and Opportunity for Translational and Industrial Research in Healthcare

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