Stem cell-derived porcine macrophages as a new platform for studying host-pathogen interactions

Background Infectious diseases of farmed and wild animals pose a recurrent threat to food security and human health. The macrophage, a key component of the innate immune system, is the first line of defence against many infectious agents and plays a major role in shaping the adaptive immune response. However, this phagocyte is a target and host for many pathogens. Understanding the molecular basis of interactions between macrophages and pathogens is therefore crucial for the development of effective strategies to combat important infectious diseases. Results We explored how porcine pluripotent stem cells (PSCs) can provide a limitless in vitro supply of genetically and experimentally tractable macrophages. Porcine PSC-derived macrophages (PSCdMs) exhibited molecular and functional characteristics of ex vivo primary macrophages and were productively infected by pig pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV) and African swine fever virus (ASFV), two of the most economically important and devastating viruses in pig farming. Moreover, porcine PSCdMs were readily amenable to genetic modification by CRISPR/Cas9 gene editing applied either in parental stem cells or directly in the macrophages by lentiviral vector transduction. Conclusions We show that porcine PSCdMs exhibit key macrophage characteristics, including infection by a range of commercially relevant pig pathogens. In addition, genetic engineering of PSCs and PSCdMs affords new opportunities for functional analysis of macrophage biology in an important livestock species. PSCs and differentiated derivatives should therefore represent a useful and ethical experimental platform to investigate the genetic and molecular basis of host-pathogen interactions in pigs, and also have wider applications in livestock.

The evolution of regulated cell death pathways in animals and their evasion by pathogens

The coevolution of host-pathogen interactions underlies many human physiological traits associated with protection from or susceptibility to infections. Among the mechanisms that animals utilize to control infections are the regulated cell death pathways of pyroptosis, apoptosis, and necroptosis. Over the course of evolution these pathways have become intricate and complex, coevolving with microbes that infect animal hosts. Microbes, in turn, have evolved strategies to interfere with the pathways of regulated cell death to avoid eradication by the host. Here, we present an overview of the mechanisms of regulated cell death in Animalia and the strategies devised by pathogens to interfere with these processes. We review the molecular pathways of regulated cell death, their roles in infection, and how they are perturbed by viruses and bacteria, providing insights into the coevolution of host-pathogen interactions and cell death pathways.

Functional Genomics and Comparative Lineage-Specific Region Analyses Reveal Novel Insights into Race Divergence in Verticillium dahliae

Deciphering the gene-for-gene relationships during host-pathogen interactions is the basis of modern plant resistance breeding. In the Verticillium dahliae -tomato pathosystem, two races (races 1 and 2) and their corresponding avirulence ( Avr ) genes have been identified, but strains that lacked these two Avr genes exist in nature.

Pathogen-Host Interaction Repertoire at Proteome and Posttranslational Modification Levels During Fungal Infections

Prevalence of fungal diseases has increased globally in recent years, which often associated with increased immunocompromised patients, aging populations, and the novel Coronavirus pandemic. Furthermore, due to the limitation of available antifungal agents mortality and morbidity rates of invasion fungal disease remain stubbornly high, and the emergence of multidrug-resistant fungi exacerbates the problem. Fungal pathogenicity and interactions between fungi and host have been the focus of many studies, as a result, lots of pathogenic mechanisms and fungal virulence factors have been identified. Mass spectrometry (MS)-based proteomics is a novel approach to better understand fungal pathogenicities and host–pathogen interactions at protein and protein posttranslational modification (PTM) levels. The approach has successfully elucidated interactions between pathogens and hosts by examining, for example, samples of fungal cells under different conditions, body fluids from infected patients, and exosomes. Many studies conclude that protein and PTM levels in both pathogens and hosts play important roles in progression of fungal diseases. This review summarizes mass spectrometry studies of protein and PTM levels from perspectives of both pathogens and hosts and provides an integrative conceptual outlook on fungal pathogenesis, antifungal agents development, and host–pathogen interactions.

Dissecting Host-Pathogen Interactions in TB Using Systems-Based Omic Approaches

Tuberculosis (TB) is a devastating infectious disease that kills over a million people every year. There is an increasing burden of multi drug resistance (MDR) and extensively drug resistance (XDR) TB. New and improved therapies are urgently needed to overcome the limitations of current treatment. The causative agent, Mycobacterium tuberculosis (Mtb) is one of the most successful pathogens that can manipulate host cell environment for adaptation, evading immune defences, virulence, and pathogenesis of TB infection. Host-pathogen interaction is important to establish infection and it involves a complex set of processes. Metabolic cross talk between the host and pathogen is a facet of TB infection and has been an important topic of research where there is growing interest in developing therapies and drugs that target these interactions and metabolism of the pathogen in the host. Mtb scavenges multiple nutrient sources from the host and has adapted its metabolism to survive in the intracellular niche. Advancements in systems-based omic technologies have been successful to unravel host-pathogen interactions in TB. In this review we discuss the application and usefulness of omics in TB research that provides promising interventions for developing anti-TB therapies.