Infectious diseases are caused by microorganisms such as viruses, bacteria, fungi, and parasites that invade and multiply in the host organism. They are a major threat to human health and well-being, especially in developing countries where they account for a large proportion of morbidity and mortality. Infectious diseases are also constantly evolving and adapting to new environments, hosts, and treatments, posing challenges for diagnosis, prevention, and control.

One of the ways to understand the molecular mechanisms of infectious diseases and to develop novel strategies for combating them is to study the transcriptome, which is the set of all RNA molecules expressed in a cell or tissue at a given time. Transcriptomics is the branch of omics that deals with the analysis of the transcriptome using high-throughput technologies such as microarrays and RNA sequencing (RNA-seq). Transcriptomics can reveal the dynamic changes in gene expression that occur during host-pathogen interactions, reflecting the host immune response and the pathogen virulence factors. Transcriptomics can also identify biomarkers for diagnosis, prognosis, and treatment response, as well as potential targets for drug discovery and vaccine development.

In this blog, we will discuss how transcriptomics can be applied to study various aspects of infectious diseases, such as:

• The host immune response and its modulation by pathogens
• The pathogen adaptation and evasion strategies
• The spatial and temporal heterogeneity of infection
• The impact of infection on host metabolism and physiology
• The discovery of novel therapeutic interventions

We will also highlight some of the challenges and limitations of transcriptomics, as well as the future directions and opportunities for this field.

The host immune response and its modulation by pathogens

The host immune system serves as the primary defense against infectious agents, encompassing innate and adaptive components that collaborate to recognize, eliminate, and memorize pathogens. It also regulates the inflammatory response crucial for infection clearance but with potential for tissue damage. Transcriptomics, a tool in molecular analysis, unveils insights into immune response mechanisms. It identifies differentially expressed genes in immune cells during infection, revealing activation or suppression of specific pathways. Additionally, transcriptomics delineates immune cell subsets and their polarization states, aiding in understanding infection outcomes. It elucidates host factors influencing susceptibility, such as genetic variants and microbiome composition. Transcriptomics’ applications extend to biomarker discovery for diagnosis, prognosis, and treatment response, differentiating bacterial and viral infections. It predicts infection severity, progression, complications, and mortality risk. Moreover, transcriptomics contributes to drug and vaccine development by pinpointing essential genes as potential targets and identifying antigens for vaccine candidates. It optimizes vaccine design and delivery, aiding in the development of effective immunomodulatory drugs.

The pathogen adaptation and evasion strategies

The pathogen is the other key player in the host-pathogen interaction. It has evolved various strategies to adapt to and evade the host immune system, such as by mutating, recombining, switching, or hiding its antigens, by modulating its gene expression, by secreting toxins or effectors, by forming biofilms or intracellular niches, or by manipulating the host signaling pathways.

• Insights through Transcriptomics: Transcriptomics reveals pathogen genes differentially expressed under diverse environmental conditions, detecting genetic variations and interactions with host elements like receptors and co-expression networks.
• Biomarker Identification: Transcriptomics aids in identifying biomarkers for pathogen diagnosis, typing, and tracking, offering insights into species, strains, and transmission routes. It also assesses drug resistance, virulence, and emergence of new variants.
• Drug and Vaccine Targets: Transcriptomics identifies essential genes for pathogen survival or host susceptibility, guiding drug discovery. It also pinpoints antigens for vaccine development, optimizing design and delivery strategies for effective drugs and vaccines.

The spatial and temporal heterogeneity of infection

The infection is not a static or homogeneous process, but rather a dynamic and heterogeneous one. It involves spatial and temporal variations in the distribution, abundance, and activity of the pathogen and the host cells and molecules, as well as in the environmental factors and stimuli. These variations can affect the course and outcome of infection, as well as the response to treatment and prevention.

• Spatial and Temporal Insights: Transcriptomics maps spatial distribution using techniques like in situ hybridization and fluorescence in situ sequencing. It also monitors temporal changes through time-series analysis and single-cell transcriptomics, capturing diversity among individuals or species.
• Diagnostic and Prognostic Biomarkers: Transcriptomics aids in biomarker discovery, detecting and localizing pathogens and host interactions. It provides information on infection extent, severity, and stage, predicting changes and dynamics during infection.
• Targets for Drug and Vaccine Development: Transcriptomics identifies differentially expressed genes in infected tissues, offering potential drug targets or vaccine candidates. It also helps optimize drug and vaccine design based on spatial and temporal infection characteristics.

The impact of infection on host metabolism and physiology

The infection is not only a molecular or cellular phenomenon, but also a systemic one. It affects the whole host metabolism and physiology, as well as the interactions with other organisms, such as the microbiota. The infection can alter the host energy balance, nutrient uptake, hormone levels, circadian rhythms, and behavior, which can have profound consequences for the host health and survival.

• Insights into Host Adaptations: Transcriptomics reveals infection-induced changes in gene expression across host tissues and organs, reflecting metabolic and physiological adaptations. It also uncovers alterations in host microbiota gene expression, influencing metabolism and immunity through various mechanisms.
• Biomarker Discovery: Transcriptomics aids in identifying biomarkers for infection diagnosis, prognosis, and treatment response by quantifying metabolic and physiological changes, such as variations in glucose, lipid, amino acid, and hormone levels. It predicts and monitors outcomes like sepsis, cachexia, organ failure, and death, associated with specific gene expression profiles.
• Targets for Intervention: Transcriptomics identifies genes involved in infection-affected metabolic pathways and host-microbiota interactions, serving as targets for drug and vaccine development. It optimizes interventions by selecting conditions, formulations, and routes based on host and microbiota gene expression profiles.

Conclusion

In this blog, we have discussed how transcriptomics can be applied to study various aspects of infectious diseases, such as the host immune response and its modulation by pathogens, the pathogen adaptation and evasion strategies, the spatial and temporal heterogeneity of infection, and the impact of infection on host metabolism and physiology. We have also highlighted some of the applications, challenges, and limitations of transcriptomics, as well as the future directions and opportunities for this field. Transcriptomics is a powerful and versatile tool that can provide a comprehensive and dynamic view of the host-pathogen interaction at the molecular level, as well as the host-microbiota interaction and the host systemic response. Transcriptomics can also facilitate the discovery and development of novel diagnostic, prognostic, and therapeutic approaches for infectious diseases, as well as the optimization and personalization of existing ones. Transcriptomics is therefore an essential component of the omics revolution that is transforming the field of infectious diseases and opening new horizons for research and innovation.

References

(1) Metabolic Host Response to Intracellular Infections.
https://link.springer.com/chapter/10.1007/978-3-319-74932-7_8
(2) Frontiers | Virus Infections and Host Metabolism—Can We Manage the Interactions? https://www.frontiersin.org/articles/10.3389/fimmu.2020.594963/full
(3) Frontiers | Metabolic host responses to infection by intracellular bacterial pathogens. https://www.frontiersin.org/articles/10.3389/fcimb.2013.00024/full