Structural implication of the induced immune response by Bacillus thuringiensis Cry proteins: role of the N-terminal region

2004 ◽  
Vol 41 (12) ◽  
pp. 1177-1183 ◽  
Author(s):  
Gloria Guillermina Guerrero ◽  
Donald H. Dean ◽  
Leticia Moreno-Fierros
Keyword(s):  
Immune Response ◽  
Bacillus Thuringiensis ◽  
Terminal Region ◽  
Cry Proteins

scholarly journals From Commensal to Pathogen: Translocation of Enterococcus faecalis from the Midgut to the Hemocoel of Manduca sexta

mBio ◽  
2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Katie L. Mason ◽  
Taylor A. Stepien ◽  
Jessamina E. Blum ◽  
Jonathan F. Holt ◽  
Normand H. Labbe ◽  
...  
Keyword(s):  
Immune Response ◽  
Gastrointestinal Tract ◽  
Bacillus Thuringiensis ◽  
Mortality Rate ◽  
Enterococcus Faecalis ◽  
Manduca Sexta ◽  
Insecticidal Toxin ◽  
Content Type ◽  
Robust Immune Response

ABSTRACTA dynamic homeostasis is maintained between the host and native bacteria of the gastrointestinal tract in animals, but migration of bacteria from the gut to other organs can lead to disease or death.Enterococcus faecalisis a commensal of the gastrointestinal tract; however,Enterococcusspp. are increasingly frequent causes of nosocomial infections with a high mortality rate. We investigated the commensal-to-pathogen switch undergone byE. faecalisOG1RF in the lepidopteran model hostManduca sextaassociated with its location in the host.E. faecalispersists in the harsh midgut environment ofM. sextalarvae without causing apparent illness, but injection ofE. faecalisdirectly into the larval hemocoel is followed by rapid death. Additionally, oral ingestion ofE. faecalisin the presence ofBacillus thuringiensisinsecticidal toxin, a pore-forming toxin that targets the midgut epithelium, induces an elevated mortality rate. We show that the loss of gut integrity due toB. thuringiensistoxin correlates with the translocation ofE. faecalisfrom the gastrointestinal tract into the hemolymph. Upon gaining access to the hemolymph,E. faecalisinduces an innate immune response, illustrated by hemocyte aggregation, in larvae prior to death. The degree of hemocyte aggregation is dependent upon the route ofE. faecalisentry. Our data demonstrate the efficacy of theM. sextalarval model system in investigatingE. faecalis-induced sepsis and clarifies controversies in the field regarding the events leading to larval death followingB. thuringiensistoxin exposure.IMPORTANCEThis study advances our knowledge ofEnterococcus faecalis-induced sepsis following translocation from the gut and provides a model for mammalian diseases in which the spatial distribution of bacteria determines disease outcomes. We demonstrate thatE. faecalisis a commensal in the gut ofManduca sextaand a pathogen in the hemocoel, resulting in a robust immune response and rapid death, a process we refer to as the “commensal-to-pathogen” switch. While controversy remains regardingBacillus thuringiensistoxin-induced killing, our laboratory previously found that under some conditions, the midgut microbiota is essential forB. thuringiensistoxin killing ofLymantria dispar(N. A. Broderick, K. F. Raffa, and J. Handelsman, Proc. Natl. Acad. Sci. U. S. A. 103:15196–15199, 2006; B. Raymond, et al., Environ. Microbiol. 11:2556–2563, 2009; P. R. Johnston, and N. Crickmore, Appl. Environ. Microbiol. 75:5094–5099, 2009). We and others have demonstrated that the role of the midgut microbiota inB. thuringiensistoxin killing is dependent upon the lepidopteran species and formulation ofB. thuringiensistoxin (N. A. Broderick, K. F. Raffa, and J. Handelsman, Proc. Natl. Acad. Sci. U. S. A. 103:15196–15199, 2006; N. A. Broderick, et al., BMC Biol. 7:11, 2009). This work reconciles much of the apparently contradictory previous data and reveals that theM. sexta-E. faecalissystem provides a model for mammalian sepsis.

scholarly journals Investigating the Properties of Bacillus thuringiensis Cry Proteins with Novel Loop Replacements Created Using Combinatorial Molecular Biology

2008 ◽  
Vol 74 (11) ◽  
pp. 3497-3511 ◽  
Author(s):  
Craig R. Pigott ◽  
Martin S. King ◽  
David J. Ellar
Keyword(s):  
Bacillus Thuringiensis ◽  
Important Determinant ◽  
Large Family ◽  
Cry Proteins ◽  
Diverse Range ◽  
The Family ◽  
Complementarity Determining Regions ◽  
Apical Loop ◽  
Loop 2

ABSTRACTCry proteins are a large family of crystalline toxins produced byBacillus thuringiensis. Individually, the family members are highly specific, but collectively, they target a diverse range of insects and nematodes. Domain II of the toxins is important for target specificity, and three loops at its apex have been studied extensively. There is considerable interest in determining whether modifications in this region may lead to toxins with novel specificity or potency. In this work, we studied the effect of loop substitution on toxin stability and specificity. For this purpose, sequences derived from antibody complementarity-determining regions (CDR) were used to replace native domain II apical loops to create “Crybodies.” Each apical loop was substituted either individually or in combination with a library of third heavy-chain CDR (CDR-H3) sequences to create seven distinct Crybody types. An analysis of variants from each library indicated that the Cry1Aa framework can tolerate considerable sequence diversity at all loop positions but that some sequence combinations negatively affect structural stability and protease sensitivity. CDR-H3 substitution showed that loop position was an important determinant of insect toxicity: loop 2 was essential for activity, whereas the effects of substitutions at loop 1 and loop 3 were sequence dependent. Unexpectedly, differences in toxicity did not correlate with binding to cadherins—a major class of toxin receptors—since all Crybodies retained binding specificity. Collectively, these results serve to better define the role of the domain II apical loops as determinants of specificity and establish guidelines for their modification.

scholarly journals Importance of Cry Proteins in Biotechnology: Initially a Bioinsecticide, Now a Vaccine Adjuvant

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 999
Author(s):  
Maria Cristina Gonzalez-Vazquez ◽  
Ruth Abril Vela-Sanchez ◽  
Norma Elena Rojas-Ruiz ◽  
Alejandro Carabarin-Lima
Keyword(s):  
Immune Response ◽  
Bacillus Thuringiensis ◽  
Specific Antigen ◽  
Structural Homology ◽  
Insect Larvae ◽  
Cry Protein ◽  
Parasporal Crystal ◽  
Cry Proteins ◽  
Experimental Animal Models ◽  
Specific Antigens

A hallmark of Bacillus thuringiensis bacteria is the formation of one or more parasporal crystal (Cry) proteins during sporulation. The toxicity of these proteins is highly specific to insect larvae, exerting lethal effects in different insect species but not in humans or other mammals. The aim of this review is to summarize previous findings on Bacillus thuringiensis, including the characteristics of the bacterium, its subsequent contribution to biotechnology as a bioinsecticide due to the presence of Cry proteins, and its potential application as an adjuvant. In several studies, Cry proteins have been administered together with specific antigens to immunize experimental animal models. The results have shown that these proteins can enhance immunogenicity by generating an adequate immune response capable of protecting the model against an experimental infectious challenge, whereas protection is decreased when the specific antigen is administered without the Cry protein. Therefore, based on previous results and the structural homology between Cry proteins, these molecules have arisen as potential adjuvants in the development of vaccines for both animals and humans. Finally, a model of the interaction of Cry proteins with different components of the immune response is proposed.

Vitamin A: dietologist’s position

2020 ◽  
pp. 49-57
Author(s):  
S. V. Orlova ◽  
E. A. Nikitina ◽  
L. I. Karushina ◽  
Yu. A. Pigaryova ◽  
O. E. Pronina
Keyword(s):  
Immune Response ◽  
Urinary Tract ◽  
Gastrointestinal Tract ◽  
Vitamin A ◽  
Developed Countries ◽  
Therapeutic Practice ◽  
The Past ◽  
Increased Risk ◽  
Mucous Membranes

Vitamin A (retinol) is one of the key elements for regulating the immune response and controls the division and differentiation of epithelial cells of the mucous membranes of the bronchopulmonary system, gastrointestinal tract, urinary tract, eyes, etc. Its significance in the context of the COVID‑19 pandemic is difficult to overestimate. However, a number of studies conducted in the past have associated the additional intake of vitamin A with an increased risk of developing cancer, as a result of which vitamin A was practically excluded from therapeutic practice in developed countries. Our review highlights the role of vitamin A in maintaining human health and the latest data on its effect on the development mechanisms of somatic pathology.

Practical consensus recommendations - Current role of immune response evaluation criteria in solid tumors criteria in the management of cancer patients receiving immunotherapy

2019 ◽  
Vol 4 ◽  
pp. 21-23
Author(s):  
Purvish M. Parikh ◽  
T. P. Sahoo ◽  
Randeep Singh ◽  
Bahl Ankur ◽  
Talvar Vineet ◽  
...  
Keyword(s):  
Immune Response ◽  
Solid Tumors ◽  
Evaluation Criteria ◽  
Supporting Evidence ◽  
Response Evaluation ◽  
Consensus Recommendation ◽  
Current Role ◽  
New Class ◽  
Response Evaluation Criteria

Response evaluation criteria in solid tumors (RECIST) are a method used to evaluate and document the response to cancer treatment in solid tumors. The availability of a new class of immuneoncology drugs has resulted in the need to modify RECIST criteria methodology. The first leadership immuno-oncology network (LION) master course brought together experts in oncology and immuno-oncology. Six questions were put to the experts and their opinion, supporting evidence, and experience were discussed to arrive at a practical consensus recommendation. n this nascent field, the availability of a practical consensus recommendation developed by experts in the field is of immense value to the community oncologist and other health-care consultants.

Hyperferritinaemia: An Iron Sword of Autoimmunity

2019 ◽  
Vol 25 (27) ◽  
pp. 2909-2918 ◽  
Author(s):  
Joanna Giemza-Stokłosa ◽  
Md. Asiful Islam ◽  
Przemysław J. Kotyla
Keyword(s):  
Immune Response ◽  
Macrophage Activation ◽  
Inflammatory Diseases ◽  
Acute Phase Reactant ◽  
Catastrophic Antiphospholipid Syndrome ◽  
Inflammatory Conditions ◽  
Phase Reactant ◽  
Signalling Molecule ◽  
Cytokine Synthesis

Background:: Ferritin is a molecule that plays many roles being the storage for iron, signalling molecule, and modulator of the immune response. Methods:: Different electronic databases were searched in a non-systematic way to find out the literature of interest. Results:: The level of ferritin rises in many inflammatory conditions including autoimmune disorders. However, in four inflammatory diseases (i.e., adult-onset Still’s diseases, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and sepsis), high levels of ferritin are observed suggesting it as a remarkable biomarker and pathological involvement in these diseases. Acting as an acute phase reactant, ferritin is also involved in the cytokine-associated modulator of the immune response as well as a regulator of cytokine synthesis and release which are responsible for the inflammatory storm. Conclusion:: This review article presents updated information on the role of ferritin in inflammatory and autoimmune diseases with an emphasis on hyperferritinaemic syndrome.

Is Immune Response Relevant in Interstitial Lung Disease?

2020 ◽  
Vol 16 (1) ◽  
pp. 18-27
Author(s):  
Manzoor M. Khan
Keyword(s):  
Immune Response ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Lung Fibrosis ◽  
Lymphocytic Infiltration ◽  
Therapeutic Strategies ◽  
Mediators Of Inflammation ◽  
Acquired Immune Responses ◽  
Novel Therapeutic Strategies

Interstitial lung disease, a term for a group of disorders, causes lung fibrosis, is mostly refractory to treatments and has a high death rate. After diagnosis the survival is up to 3 years but in some cases the patients live much longer. It involves a heterogenous group of lung diseases that exhibit progressive and irreversible destruction of the lung due to the formation of scars. This results in lung malfunction, disruption of gas exchange, and eventual death because of respiratory failure. The etiology of lung fibrosis is mostly unknown with a few exceptions. The major characteristics of the disease are comprised of injury of epithelial type II cells, increased apoptosis, chronic inflammation, monocytic and lymphocytic infiltration, accumulation of myofibroblasts, and inability to repair damaged tissue properly. These events result in abnormal collagen deposition and scarring. The inflammation process is mild, and the disease is primarily fibrotic driven. Immunosuppressants do not treat the disease but the evidence is evolving that both innate and acquired immune responses a well as the cytokines contribute to at least early progression of the disease. Furthermore, mediators of inflammation including cytokines are involved throughout the process of lung fibrosis. The diverse clinical outcome of the disease is due to different pattern of inflammatory markers. Nonetheless, the development of novel therapeutic strategies requires better understanding of the role of the immune response. This review highlights the role of the immune response in interstitial lung disease and considers the therapeutic strategies based on these observations. For this review several literature data sources were used to assess the role of the immune response in interstitial lung disease and to evaluate the possible therapeutic strategies for the disease.

scholarly journals Transglutaminases and Obesity in Humans: Association of F13A1 to Adipocyte Hypertrophy and Adipose Tissue Immune Response

2020 ◽  
Vol 21 (21) ◽  
pp. 8289
Author(s):  
Mari T. Kaartinen ◽  
Mansi Arora ◽  
Sini Heinonen ◽  
Aila Rissanen ◽  
Jaakko Kaprio ◽  
...  
Keyword(s):  
Immune Response ◽  
Adipose Tissue ◽  
Family Members ◽  
Enrichment Analysis ◽  
Human Adipose Tissue ◽  
Adipocyte Size ◽  
Gene Enrichment ◽  
Adipocyte Hypertrophy ◽  
Mz Twins

Transglutaminases TG2 and FXIII-A have recently been linked to adipose tissue biology and obesity, however, human studies for TG family members in adipocytes have not been conducted. In this study, we investigated the association of TGM family members to acquired weight gain in a rare set of monozygotic (MZ) twins discordant for body weight, i.e., heavy–lean twin pairs. We report that F13A1 is the only TGM family member showing significantly altered, higher expression in adipose tissue of the heavier twin. Our previous work linked adipocyte F13A1 to increased weight, body fat mass, adipocyte size, and pro-inflammatory pathways. Here, we explored further the link of F13A1 to adipocyte size in the MZ twins via a previously conducted TWA study that was further mined for genes that specifically associate to hypertrophic adipocytes. We report that differential expression of F13A1 (ΔHeavy–Lean) associated with 47 genes which were linked via gene enrichment analysis to immune response, leucocyte and neutrophil activation, as well as cytokine response and signaling. Our work brings further support to the role of F13A1 in the human adipose tissue pathology, suggesting a role in the cascade that links hypertrophic adipocytes with inflammation.

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