Cellular Immune Responses to Exotic Zoonotic Pathogens: Bridging the Gap Between Reservoir and Human Host

Abstract

Background/Objective- Zoonotic diseases of wild animal origin (exotic) pose a serious threat to global health. Such pathogens, such as SARS and MERS coronaviruses, Ebola, and Nipah viruses, often lack effective vaccines or specific treatments. Understanding the host immune response, especially cellular immunity, which plays a pivotal role in the control of intracellular infections, is crucial for the development of novel therapeutic and preventive strategies. This review aimed to synthesize and systematically analyze the available evidence on the role and mechanisms of cellular immunity in the face of exotic zoonotic pathogens.

Method - This study was conducted as a Systematic Review. Articles published between 2000 and 2023 were retrieved by searching reputable databases, including PubMed/Medline, Scopus, and Web of Science, using the combined keywords “zoonotic pathogens,” “cellular immunity,” “T cell,” “emerging diseases,” and the names of specific pathogens. Inclusion criteria included human studies and animal models that specifically examined T cell responses to these pathogens. After screening titles, abstracts, and full texts, data on known epitopes, cellular subsets, cytokine function, and the relationship of immune response to disease outcome were extracted and qualitatively synthesized.

Results- The analysis of the evidence showed that a strong and early response of cytotoxic T cells (CD8+) and T helper cells (Th1) is essential for clearing the infection and patient survival. In contrast, inadequate or delayed cellular immune responses were associated with disease severity and mortality. Also, the identification of conserved epitopes among related pathogens is a promising point for the design of universal vaccines. However, the high genetic diversity of these pathogens and their interaction with host MHC molecules is a significant challenge. Analysis of eligible studies demonstrated that a strong and early cytotoxic T cell (CD8+) response plays a crucial role in the control and clearance of infections caused by zoonotic pathogens. The rapid emergence of antiviral-specific CD8+ T cells, which are capable of producing effector cytokines such as IFN-γ and TNF-α and exerting direct cytotoxic activity, was found to be significantly associated with reduced viral load and host survival in animal models and human studies of viruses such as Ebola, SARS, and Nipah coronaviruses

Conclusion- The findings emphasize the pivotal and undeniable role of cellular immunity in protection against exotic zoonotic pathogens. Focusing on a more detailed understanding of the immunogenic epitopes of these pathogens and how they evade the immune response could pave the way for the development of T-cell-based therapies and a new generation of vaccines. Further longitudinal studies in high-risk groups are recommended to understand the full dynamics of these responses.