Essential Proteins and Functional Modules in the Host-Pathogen Interactions from Innate to Adaptive Immunity - C. albicans-zebrafish Infection Model

Author(s):  
Chia-Chou Wu ◽  
Bor-Sen Chen
2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Zhang ◽  
Lina Song ◽  
Lie Hou ◽  
Zhengfeng Cao ◽  
Wanwipa Vongsangnak ◽  
...  

Salmonella enteritidis (SE) is a pathogen that can readily infect ovarian tissues and colonize the granulosa cell layer such that it can be transmitted via eggs from infected poultry to humans in whom it can cause food poisoning. Ducks are an important egg-laying species that are susceptible to SE infection, yet the host–pathogen interactions between SE and ducks have not been thoroughly studied to date. Herein, we performed dual RNA-sequencing analyses of these two organisms in a time-resolved infection model of duck granulosa cells (dGCs) by SE. In total, 10,510 genes were significantly differentially expressed in host dGCs, and 265 genes were differentially expressed in SE over the course of infection. These differentially expressed genes (DEGs) of dGCs were enriched in the cytokine–cytokine receptor interaction pathway via KEGG analyses, and the DEGs in SE were enriched in the two-component system, bacterial secretion system, and metabolism of pathogen factors pathways as determined. A subsequent weighted gene co-expression network analysis revealed that the cytokine–cytokine receptor interaction pathway is mostly enriched at 6 h post-infection (hpi). Moreover, a number of pathogenic factors identified in the pathogen–host interaction database (PHI-base) are upregulated in SE, including genes encoding the pathogenicity island/component, type III secretion, and regulators of systemic infection. Furthermore, an intracellular network associated with the regulation of SE infection in ducks was constructed, and 16 cytokine response-related dGCs DEGs (including IL15, CD40, and CCR7) and 17 pathogenesis-related factors (including sseL, ompR, and fliC) were identified, respectively. Overall, these results not only offer new insights into the mechanisms underlying host–pathogen interactions between SE and ducks, but they may also aid in the selection of potential targets for antimicrobial drug development.


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jonas Kjellin ◽  
Maria Pränting ◽  
Frauke Bach ◽  
Roshan Vaid ◽  
Bart Edelbroek ◽  
...  

Abstract Background During infection by intracellular pathogens, a highly complex interplay occurs between the infected cell trying to degrade the invader and the pathogen which actively manipulates the host cell to enable survival and proliferation. Many intracellular pathogens pose important threats to human health and major efforts have been undertaken to better understand the host-pathogen interactions that eventually determine the outcome of the infection. Over the last decades, the unicellular eukaryote Dictyostelium discoideum has become an established infection model, serving as a surrogate macrophage that can be infected with a wide range of intracellular pathogens. In this study, we use high-throughput RNA-sequencing to analyze the transcriptional response of D. discoideum when infected with Mycobacterium marinum and Legionella pneumophila. The results were compared to available data from human macrophages. Results The majority of the transcriptional regulation triggered by the two pathogens was found to be unique for each bacterial challenge. Hallmark transcriptional signatures were identified for each infection, e.g. induction of endosomal sorting complexes required for transport (ESCRT) and autophagy genes in response to M. marinum and inhibition of genes associated with the translation machinery and energy metabolism in response to L. pneumophila. However, a common response to the pathogenic bacteria was also identified, which was not induced by non-pathogenic food bacteria. Finally, comparison with available data sets of regulation in human monocyte derived macrophages shows that the elicited response in D. discoideum is in many aspects similar to what has been observed in human immune cells in response to Mycobacterium tuberculosis and L. pneumophila. Conclusions Our study presents high-throughput characterization of D. discoideum transcriptional response to intracellular pathogens using RNA-seq. We demonstrate that the transcriptional response is in essence distinct to each pathogen and that in many cases, the corresponding regulation is recapitulated in human macrophages after infection by mycobacteria and L. pneumophila. This indicates that host-pathogen interactions are evolutionary conserved, derived from the early interactions between free-living phagocytic cells and bacteria. Taken together, our results strengthen the use of D. discoideum as a general infection model.


Apmis ◽  
2009 ◽  
Vol 117 (2) ◽  
pp. 95-107 ◽  
Author(s):  
CLAUS MOSER ◽  
MARIA VAN GENNIP ◽  
THOMAS BJARNSHOLT ◽  
PETER ØSTRUP JENSEN ◽  
BAOLERI LEE ◽  
...  

Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 82 ◽  
Author(s):  
Yenehiwot Weldearegay ◽  
Sandy Müller ◽  
Jana Hänske ◽  
Anja Schulze ◽  
Aline Kostka ◽  
...  

Respiratory infections caused by mycoplasma species in ruminants lead to considerable economic losses. Two important ruminant pathogens are Mycoplasma mycoides subsp. Mycoides (Mmm), the aetiological agent of contagious bovine pleuropneumonia and Mycoplasma mycoides subsp. capri (Mmc), which causes pneumonia, mastitis, arthritis, keratitis, and septicemia in goats. We established precision cut lung slices (PCLS) infection model for Mmm and Mmc to study host-pathogen interactions. We monitored infection over time using immunohistological analysis and electron microscopy. Moreover, infection burden was monitored by plating and quantitative real-time PCR. Results were compared with lungs from experimentally infected goats and cattle. Lungs from healthy goats and cattle were also included as controls. PCLS remained viable for up to two weeks. Both subspecies adhered to ciliated cells. However, the titer of Mmm in caprine PCLS decreased over time, indicating species specificity of Mmm. Mmc showed higher tropism to sub-bronchiolar tissue in caprine PCLS, which increased in a time-dependent manner. Moreover, Mmc was abundantly observed on pulmonary endothelial cells, indicating partially, how it causes systemic disease. Tissue destruction upon prolonged infection of slices was comparable to the in vivo samples. Therefore, PCLS represents a novel ex vivo model to study host-pathogen interaction in livestock mycoplasma.


2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Yu-Chao Wang ◽  
I-Chun Tsai ◽  
Che Lin ◽  
Wen-Ping Hsieh ◽  
Chung-Yu Lan ◽  
...  

The clinical and biological significance of the study of fungal pathogenCandida albicans(C. albicans) has markedly increased. However, the explicit pathogenic and invasive mechanisms of such host-pathogen interactions have not yet been fully elucidated. Therefore, the essential functional modules involved inC. albicans-zebrafish interactions were investigated in this study. Adopting a systems biology approach, the early-stage and late-stage protein-protein interaction (PPI) networks for bothC. albicansand zebrafish were constructed. By comparing PPI networks at the early and late stages of the infection process, several critical functional modules were identified in both pathogenic and defensive mechanisms. Functional modules inC. albicans, like those involved in hyphal morphogenesis, ion and small molecule transport, protein secretion, and shifts in carbon utilization, were seen to play important roles in pathogen invasion and damage caused to host cells. Moreover, the functional modules in zebrafish, such as those involved in immune response, apoptosis mechanisms, ion transport, protein secretion, and hemostasis-related processes, were found to be significant as defensive mechanisms duringC. albicansinfection. The essential functional modules thus determined could provide insights into the molecular mechanisms of host-pathogen interactions during the infection process and thereby devise potential therapeutic strategies to treatC. albicansinfection.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hugo F. Perini ◽  
Alane T. P. Moralez ◽  
Ricardo S. C. Almeida ◽  
Luciano A. Panagio ◽  
Admilton O. G. Junior ◽  
...  

2009 ◽  
Vol 53 (6) ◽  
pp. 2605-2609 ◽  
Author(s):  
Anton Y. Peleg ◽  
Sebastian Jara ◽  
Divya Monga ◽  
George M. Eliopoulos ◽  
Robert C. Moellering ◽  
...  

ABSTRACT Nonmammalian model systems of infection such as Galleria mellonella (caterpillars of the greater wax moth) have significant logistical and ethical advantages over mammalian models. In this study, we utilize G. mellonella caterpillars to study host-pathogen interactions with the gram-negative organism Acinetobacter baumannii and determine the utility of this infection model to study antibacterial efficacy. After infecting G. mellonella caterpillars with a reference A. baumannii strain, we observed that the rate of G. mellonella killing was dependent on the infection inoculum and the incubation temperature postinfection, with greater killing at 37°C than at 30°C (P = 0.01). A. baumannii strains caused greater killing than the less-pathogenic species Acinetobacter baylyi and Acinetobacter lwoffii (P < 0.001). Community-acquired A. baumannii caused greater killing than a reference hospital-acquired strain (P < 0.01). Reduced levels of production of the quorum-sensing molecule 3-hydroxy-C12-homoserine lactone caused no change in A. baumannii virulence against G. mellonella. Treatment of a lethal A. baumannii infection with antibiotics that had in vitro activity against the infecting A. baumannii strain significantly prolonged the survival of G. mellonella caterpillars compared with treatment with antibiotics to which the bacteria were resistant. G. mellonella is a relatively simple, nonmammalian model system that can be used to facilitate the in vivo study of host-pathogen interactions in A. baumannii and the efficacy of antibacterial agents.


Author(s):  
Victor Garcia-Bustos ◽  
Amparo Ruiz-Saurí ◽  
Alba Ruiz-Gaitán ◽  
Ignacio Antonio Sigona-Giangreco ◽  
Marta Dafne Cabañero-Navalon ◽  
...  

Candida auris is an emergent fungus that has become a global threat due to its multidrug resistance, mortality, and transmissibility. These unique features make it different from other Candida species, but we still do not fully know the degree of virulence and, especially, the host-pathogen interactions.


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