Lipid Body–Phagosome Interaction in Macrophages during Infectious Diseases: Host Defense or Pathogen Survival Strategy?

Phagocytosis of invading microorganisms by specialized cells such as macrophages and neutrophils is a key component of the innate immune response. These cells capture and engulf pathogens and subsequently destroy them in intracellular vacuoles—the phagosomes. Pathogen phagocytosis and progression and maturation of pathogen-containing phagosomes, a crucial event to acquire microbicidal features, occurs in parallel with accentuated formation of lipid-rich organelles, termed lipid bodies (LBs), or lipid droplets. Experimental and clinical infections with different pathogens such as bacteria, parasites, and viruses induce LB accumulation in cells from the immune system. Within these cells, LBs synthesize and store inflammatory mediators and are considered structural markers of inflammation. In addition to LB accumulation, interaction of these organelles with pathogen-containing phagosomes has increasingly been recognized in response to infections and may have implications in the outcome or survival of the microorganism within host cells. In this review, we summarize our current knowledge on the LB-phagosome interaction within cells from the immune system, with emphasis on macrophages, and discuss the functional meaning of this event during infectious diseases.     

HIV Infection Disrupts the Sympatric Host–Pathogen Relationship in Human Tuberculosis

The phylogeographic population structure of Mycobacterium tuberculosis suggests local adaptation to sympatric human populations. We hypothesized that HIV infection, which induces immunodeficiency, will alter the sympatric relationship between M. tuberculosis and its human host. To test this hypothesis, we performed a nine-year nation-wide molecular-epidemiological study of HIV–infected and HIV–negative patients with tuberculosis (TB) between 2000 and 2008 in Switzerland. We analyzed 518 TB patients of whom 112 (21.6%) were HIV–infected and 233 (45.0%) were born in Europe. We found that among European-born TB patients, recent transmission was more likely to occur in sympatric compared to allopatric host–pathogen combinations (adjusted odds ratio [OR] 7.5, 95% confidence interval [95% CI] 1.21–infinity, p = 0.03). HIV infection was significantly associated with TB caused by an allopatric (as opposed to sympatric) M. tuberculosis lineage (OR 7.0, 95% CI 2.5–19.1, p<0.0001). This association remained when adjusting for frequent travelling, contact with foreigners, age, sex, and country of birth (adjusted OR 5.6, 95% CI 1.5–20.8, p = 0.01). Moreover, it became stronger with greater immunosuppression as defined by CD4 T-cell depletion and was not the result of increased social mixing in HIV–infected patients. Our observation was replicated in a second independent panel of 440 M. tuberculosis strains collected during a population-based study in the Canton of Bern between 1991 and 2011. In summary, these findings support a model for TB in which the stable relationship between the human host and its locally adapted M. tuberculosis is disrupted by HIV infection.     

Genetic Mechanisms of Host–Pathogen Interactions for Charcoal Rot in Soybean

Soybean is a leading agronomic crop and contributes to food and agricultural security with expanding production areas in diverse regions around the world. Although soybean is challenged by several diseases and pests and progress has been made in understanding and managing some of these pathogens and pests, charcoal rot, incited by the soil-borne fungal pathogen Macrophomina phaseolina, has received little attention. M. phaseolina has a broad host range and is capable of attacking and infecting several groups of plant species, including soybean. Charcoal rot symptoms on soybean appear more commonly during hot and dry weather conditions, and are associated with drought stress. In recent years, it has become more important to develop management strategies to control charcoal rot in soybean fields. Understanding the genetics of this pathogen as well as its interactions with plant hosts will help in developing effective control and management strategies. The biology of M. phaseolina, its genetics, and plant–fungal relationships are reviewed herein. In addition, a discussion of potential opportunities utilizing modern tools to enhance genetic resistance against charcoal rot is also presented.     

Uncovering New Pathogen–Host Protein–Protein Interactions by Pairwise Structure Similarity

Pathogens usually evade and manipulate host-immune pathways through pathogen–host protein–protein interactions (PPIs) to avoid being killed by the host immune system. Therefore, uncovering pathogen–host PPIs is critical for determining the mechanisms underlying pathogen infection and survival. In this study, we developed a computational method, which we named pairwise structure similarity (PSS)-PPI, to predict pathogen–host PPIs. First, a high-quality and non-redundant structure–structure interaction (SSI) template library was constructed by exhaustively exploring heteromeric protein complex structures in the PDB database. New interactions were then predicted by searching for PSS with complex structures in the SSI template library. A quantitative score named the PSS score, which integrated structure similarity and residue–residue contact-coverage information, was used to describe the overall similarity of each predicted interaction with the corresponding SSI template. Notably, PSS-PPI yielded experimentally confirmed pathogen–host PPIs of human immunodeficiency virus type 1 (HIV-1) with performance close to that of in vitro high-throughput screening approaches. Finally, a pathogen–host PPI network of human pathogen Mycobacterium tuberculosis, the causative agent of tuberculosis, was constructed using PSS-PPI and refined using filtration steps based on cellular localization information. Analysis of the resulting network indicated that secreted proteins of the STPK, ESX-1, and PE/PPE family in M. tuberculosis targeted human proteins involved in immune response and phagocytosis. M. tuberculosis also targeted host factors known to regulate HIV replication. Taken together, our findings provide insights into the survival mechanisms of M. tuberculosis in human hosts, as well as co-infection of tuberculosis and HIV. With the rapid pace of three-dimensional protein structure discovery, the SSI template library we constructed and the PSS-PPI method we devised can be used to uncover new pathogen–host PPIs in the future.     

Scedosporium Cell Wall: From Carbohydrate-Containing Structures to Host–Pathogen Interactions

Scedosporium species are filamentous fungi usually found in sewage and soil from human-impacted areas. They cause a wide range of diseases in humans, from superficial infections, such as mycetoma, to invasive and disseminated cases, especially associated in immunocompromised patients. Scedosporium species are also related to lung colonization in individuals presenting cystic fibrosis and are considered one of the most frequent fungal pathogens associated to this pathology. Scedosporium cell wall contains glycosylated molecules involved in important biological events related to virulence and pathogenicity and represents a significant source of antigens. Polysaccharides, peptidopolysaccharides, O-linked oligosaccharides and glycosphingolipids have been identified on the Scedosporium surface. Their primary structures were determined based on a combination of techniques including gas chromatography, ESI-MS, and ¹H and ¹³C nuclear magnetic resonance. Peptidorhamnnomannans are common cell wall components among Scedosporium species. Comparing different species, minor structural differences in the carbohydrate portions were detected which could be useful to understand variations in virulence observed among the species. N- and O-linked peptidorhamnomannans are major pathogen-associated molecular patterns and, along with α-glucans, play important roles in triggering host innate immunity. Glycosphingolipids, such as glucosylceramides, have highly conserved structures in Scedosporium species and are crucial for fungal growth and virulence. The present review presents current knowledge on structural and functional aspects of Scedosporium glycoconjugates that are relevant for understanding pathogenicity mechanisms and could contribute to the design of new agents capable of inhibiting growth and differentiation of Scedosporium species. Other cell components such as melanin and ectophosphatases will be also included.

     

Altered Host Cell–Bacteria Interaction due to Nanoparticle Interaction with a Bacterial Biofilm

Nanoparticle (NP) use in everyday applications creates the potential for NPs to enter the environment where, in aquatic systems, they are likely to settle on substrates and interact with microbial communities. Legionella pneumophila biofilms are found as part of microbial communities in both natural and man-made environments, especially in man-made cooling systems. The bacterium is the causative agent of Legionnaires' disease. Legionella requires a host cell for replication in the environment, and amoebae commonly serve as this host cell. Our previous work demonstrated significant changes in Legionella biofilm morphology after exposure to 0.7 μg/L gold NPs (AuNPs). Here, we investigate how these morphology changes alter host–bacteria interactions using Acanthamoeba polyphaga as a model. Host–bacteria–NP interactions are affected by NP characteristics. Biofilms exposed to 4- and 18-nm, citrate-capped, spherical AuNPs significantly altered the grazing ability of A. polyphaga, which was not observed in biofilms exposed to 24-nm polystyrene beads. Uptake and replication of NP-exposed planktonic L. pneumophila within A. polyphaga were not altered regardless of NP size or core chemistry. Nanomaterial effects on the interaction of benthic organisms and bacteria may be directly or, as shown here, indirectly dependent on bacterial morphology. NP contamination therefore may alter interactions in a normal ecosystem function.     

Epigenetics of Host–Pathogen Interactions: The Road Ahead and the Road Behind

A growing body of evidence points towards epigenetic mechanisms being responsible for a wide range of biological phenomena, from the plasticity of plant growth and development to the nutritional control of caste determination in honeybees and the etiology of human disease (e.g., cancer). With the (partial) elucidation of the molecular basis of epigenetic variation and the heritability of certain of these changes, the field of evolutionary epigenetics is flourishing. Despite this, the role of epigenetics in shaping host–pathogen interactions has received comparatively little attention. Yet there is plenty of evidence supporting the implication of epigenetic mechanisms in the modulation of the biological interaction between hosts and pathogens. The phenotypic plasticity of many key parasite life-history traits appears to be under epigenetic control. Moreover, pathogen-induced effects in host phenotype may have transgenerational consequences, and the bases of these changes and their heritability probably have an epigenetic component. The significance of epigenetic modifications may, however, go beyond providing a mechanistic basis for host and pathogen plasticity. Epigenetic epidemiology has recently emerged as a promising area for future research on infectious diseases. In addition, the incorporation of epigenetic inheritance and epigenetic plasticity mechanisms to evolutionary models and empirical studies of host–pathogen interactions will provide new insights into the evolution and coevolution of these associations. Here, we review the evidence available for the role epigenetics on host–pathogen interactions, and the utility and versatility of the epigenetic technologies available that can be cross-applied to host–pathogen studies. We conclude with recommendations and directions for future research on the burgeoning field of epigenetics as applied to host–pathogen interactions.     

Host–parasite interactions in vector-borne protozoan infections

Protists embrace many species, some of which may be either occasional or permanent parasites of vertebrate animals. Between the parasite species, several of medical and veterinary importance are vector-transmitted. The ecology and epidemiology of vector-borne parasitoses, including babesiosis, leishmaniasis and malaria, are particularly complex, as they are influenced by many factors, such as vector reproductive efficiency and geographical spread, vectorial capacity, host immunity, travel and human behaviour and climatic factors. Transmission dynamics are determined by the interactions between pathogen, vector, host and environmental factors and, given their complexity, many different types of mathematical models have been developed to understand them. A good basic knowledge of vector-pathogen relationships and transmission dynamics is thus essential for disease surveillance and control interventions and may help in understanding the spread of epidemics and be useful for public health planning.     

Trichoderma–Plant–Pathogen Interactions: Advances in Genetics of Biological Control

Trichoderma spp. are widely used in agriculture as biofungicides. Induction of plant defense and mycoparasitism (killing of one fungus by another) are considered to be the most important mechanisms of Trichoderma-mediated biological control. Understanding these mechanisms at the molecular level would help in developing strains with superior biocontrol properties. In this article, we review our current understanding of the genetics of interactions of Trichoderma with plants and plant pathogens.     

Nitric Oxide Production by Necrotrophic Pathogen Macrophomina phaseolina and the Host Plant in Charcoal Rot Disease of Jute: Complexity of the Interplay between Necrotroph–Host Plant Interactions

M. phaseolina, a global devastating necrotrophic fungal pathogen causes charcoal rot disease in more than 500 host plants. With the aim of understanding the plant-necrotrophic pathogen interaction associated with charcoal rot disease of jute, biochemical approach was attempted to study cellular nitric oxide production under diseased condition. This is the first report on M. phaseolina infection in Corchorus capsularis (jute) plants which resulted in elevated nitric oxide, reactive nitrogen species and S nitrosothiols production in infected tissues. Time dependent nitric oxide production was also assessed with 4-Amino-5-Methylamino-2′,7′-Difluorofluorescein Diacetate using single leaf experiment both in presence of M. phaseolina and xylanases obtained from fungal secretome. Cellular redox status and redox active enzymes were also assessed during plant fungal interaction. Interestingly, M. phaseolina was found to produce nitric oxide which was detected in vitro inside the mycelium and in the surrounding medium. Addition of mammalian nitric oxide synthase inhibitor could block the nitric oxide production in M. phaseolina. Bioinformatics analysis revealed nitric oxide synthase like sequence with conserved amino acid sequences in M. phaseolina genome sequence. In conclusion, the production of nitric oxide and reactive nitrogen species may have important physiological significance in necrotrophic host pathogen interaction.     

Arms Race Coevolution: The Local and Geographical Structure of a Host–Parasite Interaction

Consideration of complex geographic patterns of reciprocal adaptation has provided insight into new features of the coevolutionary process. In this paper, we provide ecological, historical, and geographical evidence for coevolution under complex temporal and spatial scenarios that include intermittent selection, species turnover across localities, and a range of trait match/mismatch across populations. Our study focuses on a plant host–parasitic plant interaction endemic to arid and semiarid regions of Chile. The long spines of Chilean cacti have been suggested to evolve under parasite-mediated selection as a first line of defense against the mistletoe Tristerix aphyllus. The mistletoe, in turn, has evolved an extremely long morphological structure that emerges from the seed endosperm (radicle) to reach the host cuticle. When spine length was traced along cactus phylogenies, a significant association between spine length and parasitism was detected, indicating that defensive traits evolved in high correspondence with the presence or absence of parasitism in two cactus lineages. Assessment of spine-radicle matching across populations revealed a potential for coevolution in 50% of interaction pairs. Interestingly, hot spots for coevolution did not distribute at random across sites. On the contrary, interaction pairs showing high matching values occur mostly in the northern distribution of the interaction, suggesting a geographical structure for coevolution in this system. Only three sampled interaction pairs were so mismatched that reciprocal selection could not occur given current trait distributions. Overall, different lines of evidence indicate that arms-race coevolution is an ongoing phenomenon that occurs in the global system of interconnected populations.