scholarly journals Vertical Transmission of Listeria monocytogenes: Probing the Balance between Protection from Pathogens and Fetal Tolerance

Pathogens ◽  
2018 ◽  
Vol 7 (2) ◽  
pp. 52 ◽  
Author(s):  
Nicole Lamond ◽  
Nancy Freitag
Keyword(s):  
Cell Culture ◽  
Listeria Monocytogenes ◽  
Animal Models ◽  
Vertical Transmission ◽  
Surface Proteins ◽  
Placental Barrier ◽  
Bacterial Surface ◽  
Organ Models ◽  
The Many

Protection of the developing fetus from pathogens is one of the many critical roles of the placenta. Listeria monocytogenes is one of a select number of pathogens that can cross the placental barrier and cause significant harm to the fetus, leading to spontaneous abortion, stillbirth, preterm labor, and disseminated neonate infection despite antibiotic treatment. Such severe outcomes serve to highlight the importance of understanding how L. monocytogenes mediates infiltration of the placental barrier. Here, we review what is currently known regarding vertical transmission of L. monocytogenes as a result of cell culture and animal models of infection. In vitro cell culture and organ models have been useful for the identification of L. monocytogenes virulence factors that contribute to placental invasion. Examples include members of the Internalin family of bacterial surface proteins such as Interalin (Inl)A, InlB, and InlP that promote invasion of cells at the maternal-fetal interface. A number of animal models have been used to interrogate L. monocytogenes vertical transmission, including mice, guinea pigs, gerbils, and non-human primates; each of these models has advantages while still not providing a comprehensive understanding of L. monocytogenes invasion of the human placenta and/or fetus. These models do, however, allow for the molecular investigation of the balance between fetal tolerance and immune protection from L. monocytogenes during pregnancy.

scholarly journals PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes

2015 ◽  
Vol 212 (2) ◽  
pp. 165-183 ◽  
Author(s):  
Grégoire Gessain ◽  
Yu-Huan Tsai ◽  
Laetitia Travier ◽  
Matteo Bonazzi ◽  
Solène Grayo ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Critical Role ◽  
Intestinal Barrier ◽  
Surface Proteins ◽  
Target Cells ◽  
Placental Barrier ◽  
Bacterial Surface ◽  
Phosphoinositide 3 Kinase ◽  
K Activity ◽  
E Cadherin

Invasion of nonphagocytic cells, a critical property of Listeria monocytogenes (Lm) that enables it to cross host barriers, is mediated by the interaction of two bacterial surface proteins, InlA and InlB, with their respective receptors E-cadherin and c-Met. Although InlA–E-cadherin interaction is necessary and sufficient for Lm crossing of the intestinal barrier, both InlA and InlB are required for Lm crossing of the placental barrier. The mechanisms underlying these differences are unknown. Phosphoinositide 3-kinase (PI3-K) is involved in both InlA- and InlB-dependent pathways. Indeed, InlA-dependent entry requires PI3-K activity but does not activate it, whereas InlB–c-Met interaction activates PI3-K. We show that Lm intestinal target cells exhibit a constitutive PI3-K activity, rendering InlB dispensable for InlA-dependent Lm intestinal barrier crossing. In contrast, the placental barrier does not exhibit constitutive PI3-K activity, making InlB necessary for InlA-dependent Lm placental invasion. Here, we provide the molecular explanation for the respective contributions of InlA and InlB to Lm host barrier invasion, and reveal the critical role of InlB in rendering cells permissive to InlA-mediated invasion. This study shows that PI3-K activity is critical to host barrier permissiveness to microbes, and that pathogens exploit both similarities and differences of host barriers to disseminate.

scholarly journals Efficacy of Nitazoxanide againstCryptosporidium parvum in Cell Culture and in Animal Models

1998 ◽  
Vol 42 (8) ◽  
pp. 1959-1965 ◽  
Author(s):  
Cynthia M. Theodos ◽  
Jeffrey K. Griffiths ◽  
Jennifer D’Onfro ◽  
Alexandra Fairfield ◽  
Saul Tzipori
Keyword(s):  
Cell Culture ◽  
Clinical Trials ◽  
Body Weight ◽  
Animal Models ◽  
Cryptosporidium Parvum ◽  
Combined Treatment ◽  
Parasite Burden ◽  
Parasite Growth ◽  
Gnotobiotic Piglet

ABSTRACT Nitazoxanide (NTZ), a drug currently being tested in human clinical trials for efficacy against chronic cryptosporidiosis, was assessed in cell culture and in two animal models. The inhibitory activity of NTZ was compared with that of paromomycin (PRM), a drug that is partially effective against Cryptosporidium parvum. A concentration of 10 μg of NTZ/ml (32 μM) consistently reduced parasite growth in cell culture by more than 90% with little evidence of drug-associated cytotoxicity, in contrast to an 80% reduction produced by PRM at 2,000 μg/ml (3.2 mM). In contrast to its efficacy in vitro, NTZ at either 100 or 200 mg/kg of body weight/day for 10 days was ineffective at reducing the parasite burden in C. parvum-infected, anti-gamma-interferon-conditioned SCID mice. Combined treatment with NTZ and PRM was no more effective than treatment with PRM alone. Finally, NTZ was partially effective at reducing the parasite burden in a gnotobiotic piglet diarrhea model when given orally for 11 days at 250 mg/kg/day but not at 125 mg/kg/day. However, the higher dose of NTZ induced a drug-related diarrhea in piglets that might have influenced its therapeutic efficacy. As we have previously reported, PRM was effective at markedly reducing the parasite burden in piglets at a dosage of 500 mg/kg/day. Our results indicate that of all of the models tested, the piglet diarrhea model most closely mimics the partial response to NTZ treatment reported to occur in patients with chronic cryptosporidiosis.

scholarly journals Neuromuscular Development and Disease: Learning From in vitro and in vivo Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Zachary Fralish ◽  
Ethan M. Lotz ◽  
Taylor Chavez ◽  
Alastair Khodabukus ◽  
Nenad Bursac
Keyword(s):  
Skeletal Muscle ◽  
Cell Culture ◽  
Animal Models ◽  
Schwann Cells ◽  
Motor Neurons ◽  
Small Animal ◽  
In Vivo Models ◽  
Small Animal Models

The neuromuscular junction (NMJ) is a specialized cholinergic synaptic interface between a motor neuron and a skeletal muscle fiber that translates presynaptic electrical impulses into motor function. NMJ formation and maintenance require tightly regulated signaling and cellular communication among motor neurons, myogenic cells, and Schwann cells. Neuromuscular diseases (NMDs) can result in loss of NMJ function and motor input leading to paralysis or even death. Although small animal models have been instrumental in advancing our understanding of the NMJ structure and function, the complexities of studying this multi-tissue system in vivo and poor clinical outcomes of candidate therapies developed in small animal models has driven the need for in vitro models of functional human NMJ to complement animal studies. In this review, we discuss prevailing models of NMDs and highlight the current progress and ongoing challenges in developing human iPSC-derived (hiPSC) 3D cell culture models of functional NMJs. We first review in vivo development of motor neurons, skeletal muscle, Schwann cells, and the NMJ alongside current methods for directing the differentiation of relevant cell types from hiPSCs. We further compare the efficacy of modeling NMDs in animals and human cell culture systems in the context of five NMDs: amyotrophic lateral sclerosis, myasthenia gravis, Duchenne muscular dystrophy, myotonic dystrophy, and Pompe disease. Finally, we discuss further work necessary for hiPSC-derived NMJ models to function as effective personalized NMD platforms.

scholarly journals In vitro evaluation of Clostridium septicum alpha toxoid

2010 ◽  
Vol 62 (4) ◽  
pp. 778-783 ◽  
Author(s):  
F.M. Salvarani ◽  
Z.I.P. Lobato ◽  
R.A. Assis ◽  
C.G.R.D. Lima ◽  
R.O.S. Silva ◽  
...  
Keyword(s):  
Cell Culture ◽  
Animal Models ◽  
Neutralizing Antibody ◽  
Viable Alternative ◽  
Antibody Detection ◽  
Alpha Toxin ◽  
Clostridium Septicum ◽  
Vaccine Potency

Aiming to investigate in vitro alternatives, a test for neutralizing antibody detection using cell culture was developed. This test was more sensitive than previous animal models, allowing for detection of substantially lower alpha toxin and anti-alpha toxin titers. Titers observed during in vivo and in vitro seroneutralization had a correlation of 99.12%, indicating that cell culture is a viable alternative in the evaluation of vaccine potency, screening of vaccinal seeds, and Clostridium septicum alpha toxin titration.

scholarly journals The Sortase SrtA of Listeria monocytogenes Is Involved in Processing of Internalin and in Virulence

2002 ◽  
Vol 70 (3) ◽  
pp. 1382-1390 ◽  
Author(s):  
Caroline Garandeau ◽  
Hélène Réglier-Poupet ◽  
Iharilalao Dubail ◽  
Jean-Luc Beretti ◽  
Patrick Berche ◽  
...  
Keyword(s):  
Cell Wall ◽  
Listeria Monocytogenes ◽  
Protein A ◽  
Knockout Mutant ◽  
Reporter Protein ◽  
Gram Positive ◽  
Bacterial Surface ◽  
Gram Positive Bacteria ◽  
Covalently Linked

ABSTRACT Listeria monocytogenes is an intracellular gram-positive human pathogen that invades eucaryotic cells. Among the surface-exposed proteins playing a role in this invasive process, internalin belongs to the family of LPXTG proteins, which are known to be covalently linked to the bacterial cell wall in gram-positive bacteria. Recently, it has been shown in Staphylococcus aureus that the covalent anchoring of protein A, a typical LPXTG protein, is due to a cysteine protease, named sortase, required for bacterial virulence. Here, we identified in silico from the genome of L. monocytogenes a gene, designated srtA, encoding a sortase homologue. The role of this previously unknown sortase was studied by constructing a sortase knockout mutant. Internalin was used as a reporter protein to study the effects of the srtA mutation on cell wall anchoring of this LPXTG protein in L. monocytogenes. We show that the srtA mutant (i) is affected in the display of internalin at the bacterial surface, (ii) is significantly less invasive in vitro, and (iii) is attenuated in its virulence in the mouse. These results demonstrate that srtA of L. monocytogenes acts as a sortase and plays a role in the pathogenicity.

Hepatitis E Virus: Animal Models and Zoonosis

2019 ◽  
Vol 7 (1) ◽  
pp. 427-448 ◽  
Author(s):  
Scott P. Kenney ◽  
Xiang-Jin Meng
Keyword(s):  
Animal Models ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Diagnostic Techniques ◽  
Detection Methods ◽  
Extrahepatic Manifestations ◽  
Virus Shedding ◽  
The Many ◽  
Animal Strains

Hepatitis E virus (HEV) is an important human pathogen that historically has been difficult to study. Limited levels of replication in vitro hindered our understanding of the viral life cycle. Sporadic and low-level virus shedding, lack of standardized detection methods, and subclinical infections made the development of animal models difficult. Better diagnostic techniques and understanding of the virus increased our ability to identify and characterize animal strains and animals that are amenable to model human-relevant infection. These advances are translating into the development of useful HEV animal models so that some of the greatest concerns associated with HEV infection, including host immunology, chronic infection, severe pregnancy mortality, and extrahepatic manifestations, can now be studied. Continued development of these animal models will be instrumental in understanding the many complex questions associated with HEV infection and for assessing therapeutics and prevention strategies to minimize HEV becoming a greater risk to the human population.

Differentiation of Stem Cells into Neuronal Lineage: In Vitro Cell Culture and In Vivo Transplantation in Animal Models

2021 ◽  
pp. 73-102
Author(s):  
Shahid S. Siddiqui ◽  
Khaled Aboshamat ◽  
Sivakumar Loganathan ◽  
Zeba K. Siddiqui
Keyword(s):  
Stem Cells ◽  
Cell Culture ◽  
Animal Models ◽  
In Vitro Cell Culture ◽  
Neuronal Lineage
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