The prognosis of infectious diseases is determined by host-pathogen interactions. Control of pathogens has been the central dogma of treating infectious diseases in modern medicine, but the pathogen-directed medicine is facing significant challenges, including a lack of effective antimicrobials for newly emerging pathogens, pathogen drug resistance, and drug side effects. Here, a mathematic equation (termed equation of host-pathogen interactions, HPI-Equation) is developed to dissect the key variables of host-pathogen interactions. It shows that control of pathogens does not necessarily lead to host recovery. Instead, a combination of promoting a host's power of self-healing and balancing immune responses provides the best benefit for host. Moreover, the HPI-Equation elucidates the scientific basis of traditional Chinese medicine (TCM), a host-based medicine that treats infectious diseases by promoting self-healing power and balancing immune responses. The importance of self-healing power elucidated in the HPI-Equation is confirmed by recent studies that the tolerance mechanism, which is discovered in plants and animals and conceptually similar to self-healing power, improves host survival without directly attacking pathogens. In summary, the HPI-Equation describes host-pathogen interactions with mathematical logic and precision; it translates the ancient wisdoms of TCM into apprehensible modern sciences and opens a new venue for integrating TCM and modern medicine for a future medicine. Sun J. A mathematic equation derived from host-pathogen interactions elucidates the significance of integrating modern medicine with traditional Chinese medicine to treat infectious diseases. J Integr Med. 2023; 21(4):324-331.
Animals ; Medicine, Chinese Traditional ; Communicable Diseases/drug therapy* ; Mathematics ; Host-Pathogen Interactions ; Drugs, Chinese Herbal/therapeutic use*

Autophagy is an intracellular degradation process that maintains cellular homeostasis. It is essential for protecting organisms from environmental stress. Autophagy can help the host to eliminate invading pathogens, including bacteria, viruses, fungi, and parasites. However, pathogens have evolved multiple strategies to interfere with autophagic signaling pathways or inhibit the fusion of autophagosomes with lysosomes to form autolysosomes. Moreover, host cell matrix degradation by different types of autophagy can be used for the proliferation and reproduction of pathogens. Thus, determining the roles and mechanisms of autophagy during pathogen infections will promote understanding of the mechanisms of pathogen‍‒‍host interactions and provide new strategies for the treatment of infectious diseases.
Autophagy ; Bacteria ; Host-Pathogen Interactions ; Lysosomes ; Signal Transduction

Aims: Antimicrobial compounds are bioactive compounds that have ability to inhibit microbial growth activities. This study aimed to screen and identify bacteria associated with Haliclona sp. sponges from Enggano Island, Indonesia that had potential to produce antimicrobial compounds against Escherichia coli, Candida albicans and Staphylococcus epidermidis. Methodology and results: The method used to screen and identify bacteria in this study including screening assay, morphological identification, Gram staining and spore staining method, biochemical tests and molecular identification based on 16S rRNA gene. This study resulted 16 isolates which were successfully isolated from Haliclona sp. According to screening assay, 5 isolates could potentially produce antimicrobial compounds coded as HEBS1, HEBS3, HEBS6, HEBB2 and HEBB3. Based on Gram staining, spore staining, biochemical test and molecular identification results, HEBS1 had proximity to Brachybacterium paraconglomeratum, HEBS3 had proximity to Kocuria palustris, HEBS6 had proximity to Psychrobacter pasificensis, HEBB2 had proximity to Bacillus aryabhattai, and HEBB3 had proximity to Bacillus toyonensis. Conclusion, significance and impact of study From 16 isolates that successfully isolated, there were 5 isolates that could potentially produce antimicrobial compounds against Escherichia coli, Staphylococcus epidermidis and Candida albicans. These isolates can be served as antimicrobial compounds producer. However, identification and purification of these antimicrobial compounds are needed to be done before applied it for medicine in the future.
Haliclona--microbiology ; Host-Pathogen Interactions

Porcine epidemic diarrhea virus (PEDV) is a highly infectious pathogen that can cause severe diseases in pigs and result in enormous economic losses in the worldwide swine industry. Previous studies revealed that PEDV exhibits an obvious capacity for modulating interferon (IFN) signaling or expression. The newly discovered type III IFN, which plays a crucial role in antiviral immunity, has strong antiviral activity against PEDV proliferation in IPEC-J2 cells. In this study, we aimed to investigate the effect of PEDV nucleocapsid (N) protein on type III IFN-λ. We found that the N proteins of ten PEDV strains isolated between 2013 and 2017 from different local farms shared high nucleotide identities, while the N protein of the CV777 vaccine strain formed a monophyletic branch in the phylogenetic tree. The N protein of the epidemic strain could antagonize type III IFN, but not type I or type II IFN expression induced by polyinosinic-polycytidylic acid (poly(I:C)) in IPEC-J2 cells. Subsequently, we demonstrated that the inhibition of poly(I:C)-induced IFN-λ3 production by PEDV N protein was dependent on the blocking of nuclear factor-κB (NF-κB) nuclear translocation. These findings might help increase understanding of the pathogenesis of PEDV and its mechanisms for evading the host immune response.
Active Transport, Cell Nucleus ; Animals ; Coronavirus Infections ; immunology ; veterinary ; virology ; Genes, Viral ; Host-Pathogen Interactions ; immunology ; Interferons ; antagonists & inhibitors ; biosynthesis ; genetics ; Interleukins ; antagonists & inhibitors ; biosynthesis ; genetics ; NF-kappa B ; metabolism ; Nucleocapsid Proteins ; genetics ; immunology ; physiology ; Porcine epidemic diarrhea virus ; genetics ; pathogenicity ; physiology ; Promoter Regions, Genetic ; Swine ; Swine Diseases ; immunology ; virology

High-throughput transcriptomics technologies have been widely used to study plant transcriptional reprogramming during the process of plant defense responses, and a large quantity of gene expression data have been accumulated in public repositories. However, utilization of these data is often hampered by the lack of standard metadata annotation. In this study, we curated 2444 public pathogenesis-related gene expression samples from the model plant Arabidopsis and three major crops (maize, rice, and wheat). We organized the data into a user-friendly database termed as PlaD. Currently, PlaD contains three key features. First, it provides large-scale curated data related to plant defense responses, including gene expression and gene functional annotation data. Second, it provides the visualization of condition-specific expression profiles. Third, it allows users to search co-regulated genes under the infections of various pathogens. Using PlaD, we conducted a large-scale transcriptome analysis to explore the global landscape of gene expression in the curated data. We found that only a small fraction of genes were differentially expressed under multiple conditions, which might be explained by their tendency of having more network connections and shorter network distances in gene networks. Collectively, we hope that PlaD can serve as an important and comprehensive knowledgebase to the community of plant sciences, providing insightful clues to better understand the molecular mechanisms underlying plant immune responses. PlaD is freely available at http://systbio.cau.edu.cn/plad/index.php or http://zzdlab.com/plad/index.php.
Arabidopsis ; genetics ; Databases, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Gene Regulatory Networks ; Genes, Plant ; Host-Pathogen Interactions ; genetics ; Oryza ; genetics ; Plant Immunity ; genetics ; Plants ; genetics ; microbiology ; Transcriptome ; genetics ; Triticum ; genetics ; User-Computer Interface ; Zea mays ; genetics

Animals ; Bacteria ; pathogenicity ; Biological Evolution ; Host-Pathogen Interactions ; Humans ; Symbiosis

Microbiome research is a quickly developing field in biomedical research, and we have witnessed its potential in understanding the physiology, metabolism and immunology, its critical role in understanding the health and disease of the host, and its vast capacity in disease prediction, intervention and treatment. However, many of the fundamental questions still need to be addressed, including the shaping forces of microbial diversity between individuals and across time. Microbiome research falls into the classical nature vs. nurture scenario, such that host genetics shape part of the microbiome, while environmental influences change the original course of microbiome development. In this review, we focus on the nature, i.e., the genetic part of the equation, and summarize the recent efforts in understanding which parts of the genome, especially the human and mouse genome, play important roles in determining the composition and functions of microbial communities, primarily in the gut but also on the skin. We aim to present an overview of different approaches in studying the intricate relationships between host genetic variations and microbes, its underlying philosophy and methodology, and we aim to highlight a few key discoveries along this exploration, as well as current pitfalls. More evidence and results will surely appear in upcoming studies, and the accumulating knowledge will lead to a deeper understanding of what we could finally term a "hologenome", that is, the organized, closely interacting genome of the host and the microbiome.
Animals ; Biomedical Research ; Genes ; Genetic Variation ; Genome ; Host-Pathogen Interactions ; genetics ; Humans ; Metagenomics ; Microbiota

Organoid is an in vitro multicellular form mimicking in vivo organ. Its similarity to human organ including cellular organization, molecular expression patterns, as well as genetic signatures enables to study the characteristics of infectious agents and host-pathogen interaction. For the features of organoid, this system also can be potentially used to cultivate currently uncultivable viruses of vaccine candidates. This paper will briefly describe problems in the current culture system for virus production and the possibility of organoid as culture system for viral vaccine and their current limitations that should be solved to meet the goal.
Host-Pathogen Interactions ; Humans ; In Vitro Techniques ; Organoids* ; Viral Vaccines ; Virus Cultivation

Saprolegniasis is one of the most devastating oomycete diseases in freshwater fish which is caused by species in the genus Saprolegnia including Saprolegnia parasitica. In this study, we isolated the strain of S. parasitica from diseased rainbow trout in Korea. Morphological and molecular based identification confirmed that isolated oomycete belongs to the member of S. parasitica, supported by its typical features including cotton-like mycelium, zoospores and phylogenetic analysis with internal transcribed spacer region. Pathogenicity of isolated S. parasitica was developed in embryo, juvenile, and adult zebrafish as a disease model. Host-pathogen interaction in adult zebrafish was investigated at transcriptional level. Upon infection with S. parasitica, pathogen/antigen recognition and signaling (TLR2, TLR4b, TLR5b, NOD1, and major histocompatibility complex class I), pro/anti-inflammatory cytokines (interleukin [IL]-1β, tumor necrosis factor α, IL-6, IL-8, interferon γ, IL-12, and IL-10), matrix metalloproteinase (MMP9 and MMP13), cell surface molecules (CD8⁺ and CD4⁺) and antioxidant enzymes (superoxide dismutase, catalase) related genes were differentially modulated at 3- and 12-hr post infection. As an anti-Saprolegnia agent, plant based lawsone was applied to investigate on the susceptibility of S. parasitica showing the minimum inhibitory concentration and percentage inhibition of radial growth as 200 μg/mL and 31.8%, respectively. Moreover, natural lawsone changed the membrane permeability of S. parasitica mycelium and caused irreversible damage and disintegration to the cellular membranes of S. parasitica. Transcriptional responses of the genes of S. parasitica mycelium exposed to lawsone were altered, indicating that lawsone could be a potential anti-S. parasitica agent for controlling S. parasitica infection.
Adult ; Cytokines ; Embryonic Structures ; Fresh Water ; Host-Pathogen Interactions ; Humans ; Interferons ; Interleukin-12 ; Interleukin-6 ; Interleukin-8 ; Korea* ; Major Histocompatibility Complex ; Membranes ; Microbial Sensitivity Tests ; Mycelium ; Oncorhynchus mykiss* ; Oomycetes ; Permeability ; Plants ; Saprolegnia* ; Tumor Necrosis Factor-alpha ; Virulence ; Zebrafish*

Johne's disease or paratuberculosis is a chronic debilitating disease in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). The disease causes significant economic losses in livestock industries worldwide. There are no effective control measures to eradicate the disease because there are no appropriate diagnostic methods to detect subclinically infected animals. Therefore, it is very difficult to control the disease using only test and cull strategies. Vaccination against paratuberculosis has been considered as an alternative strategy to control the disease when combined with management interventions. Understanding host-pathogen interactions is extremely important to development of vaccines. It has long been known that Th1-mediated cellular immune responses are play a crucial role in protection against MAP infection. However, recent studies suggested that innate immune responses are more closely related to protective effects than adaptive immunity. Based on this understanding, several attempts have been made to develop vaccines against paratuberculosis. A variety of ideas for designing novel vaccines have emerged, and the tests of the efficacy of these vaccines are conducted constantly. However, no effective vaccines are commercially available. In this study, studies of the development of vaccines for MAP were reviewed and summarized.
Adaptive Immunity ; Animals ; Host-Pathogen Interactions ; Immunity, Cellular ; Immunity, Innate ; Livestock ; Mycobacterium avium subsp. paratuberculosis* ; Mycobacterium avium* ; Mycobacterium* ; Paratuberculosis ; Ruminants ; Vaccination ; Vaccines*