Emerging Mechanisms of Host-Pathogen Interactions and Immune Responses

Aabid Hussain^1*Haris Saeed^2*Sehbanul Islam^3*Priyadarshi Soumyaranjan Sahu^4*Arpit Kumar Shrivastava^5*

• ¹Cleveland Clinic, Cleveland, United States
• ²University of Southern California, Los Angeles, United States
• ³University of Pennsylvania, Philadelphia, United States
• ⁴Medical University of the Americas, Charlestown, Saint Kitts and Nevis
• ⁵Indian Institute of Technology Indore, Indore, India

Host-pathogen interactions are dynamic and multifaceted processes where the host detects and deploys innate and acquired immune responses to eliminate the pathogens. In contrast, pathogens employ strategies to infect, evade, and manipulate the host defenses [Finlay, B. B., et al., 2006]. Host defenses activate innate immune sensors, such as inflammasomes, toll-like receptors (TLRs), and other pattern recognition receptors (PRRs), alongside adaptive responses to identify pathogens and trigger inflammation [Kawai, T., et al., 2010]. However, many pathogens have developed strategies to suppress or escape these responses, highlighting the ongoing nature of the immunological arms race. These strategies include the subversion of autophagy alongside host responses mediated by innate immune sensors, molecular mimicry, and the release of virulence factors [Pradel, B., et al., 2020]. Microbial proteins activate signaling pathways that induce or inhibit apoptosis, contributing to disease pathogenesis [Häcker, G., et al., 2018]. Recent findings showed that non-coding RNAs, microbiome, The research article and reviews compiled in this research topic underscore the host-pathogen relationship's adaptive nature and complexity. The review articles summarize the major milestones achieved in understanding the host-microbe interaction in infectious diseases. On the other hand, the research articles identified a clear picture of how pathogens interact with the host immunity to influence the disease outcomes and identified specific pathways that can be harnessed for therapeutic purposes. For instance, cellular pathways such as apoptosis, ferroptosis, autophagy, and immune signaling mechanisms have been shown to play essential roles during infection. Although targeting autophagy presents a promising therapeutic avenue to combat infectious diseases, challenges related to host tissue damage, immune modulation, and pathogen adaptation remain unresolved. It is therefore worth exploring whether pathogenderived factors that alter inflammatory pathways may cooperate to influence host autophagy regulatory genes, potentially contributing to neuronal damage during infection [Sahu S. S., et al., 2018].Further research is needed to identify host factors essential for the pathogenesis of infectious diseases, which can be systematically uncovered using genome-wide CRISPR-Cas9 screens [Binnie, A., et al., 2021]. Complementary approaches, such as single-cell RNA-seq and quantitative proteomics, can identify key players involved in infectious diseases. These analyses can also reveal genes, signaling networks, and pathways such as apoptosis and autophagy that are manipulated by a particular pathogen [Gong, Q., et al., 2024]. In addition, high-throughput datasets on host-pathogen interactions, compiled in public databases, provide a valuable resource for understanding infection biology [Le, T.D., et al., 2024]. Altogether, integrating multi-omics, systems biology, and immunogenomics approaches can bridge critical knowledge gaps and advance next-generation precision medicine, immunotherapies, and vaccines.The virulence factors can be pharmacologically targeted to make it less virulent and cleared through the host's immune system. Similarly, the host immune system can be boosted through