scholarly journals Rickettsia-host interaction: strategies of intracytosolic host colonization

2021 ◽  
Vol 79 (4) ◽  
Author(s):  
Oliver H Voss ◽  
M Sayeedur Rahman
Keyword(s):  
Defense Mechanisms ◽  
Membrane Dynamics ◽  
Immune Defense ◽  
Mammalian Host ◽  
Phosphoinositide Metabolism ◽  
Host Colonization ◽  
Rickettsia Species ◽  
Cellular Processes ◽  
Host Interaction ◽  
Complex Biological Process

ABSTRACT Bacterial infection is a highly complex biological process involving a dynamic interaction between the invading microorganism and the host. Specifically, intracellular pathogens seize control over the host cellular processes including membrane dynamics, actin cytoskeleton, phosphoinositide metabolism, intracellular trafficking and immune defense mechanisms to promote their host colonization. To accomplish such challenging tasks, virulent bacteria deploy unique species-specific secreted effectors to evade and/or subvert cellular defense surveillance mechanisms to establish a replication niche. However, despite superficially similar infection strategies, diverse Rickettsia species utilize different effector repertoires to promote host colonization. This review will discuss our current understandings on how different Rickettsia species deploy their effector arsenal to manipulate host cellular processes to promote their intracytosolic life within the mammalian host.

scholarly journals Fibrinolysis: A Primordial System Linked to the Immune Response

2021 ◽  
Vol 22 (7) ◽  
pp. 3406
Author(s):  
Robert L. Medcalf ◽  
Charithani B. Keragala
Keyword(s):  
Binding Sites ◽  
Defense Mechanisms ◽  
Immune Cell ◽  
Immune Defense ◽  
Surface Proteins ◽  
Cell Behavior ◽  
Phylogenetic Studies ◽  
Blood Clots ◽  
Lower Vertebrates ◽  
Almost All

The fibrinolytic system provides an essential means to remove fibrin deposits and blood clots. The actual protease responsible for this is plasmin, formed from its precursor, plasminogen. Fibrin is heralded as it most renowned substrate but for many years plasmin has been known to cleave many other substrates, and to also activate other proteolytic systems. Recent clinical studies have shown that the promotion of plasmin can lead to an immunosuppressed phenotype, in part via its ability to modulate cytokine expression. Almost all immune cells harbor at least one of a dozen plasminogen receptors that allows plasmin formation on the cell surface that in turn modulates immune cell behavior. Similarly, a multitude of pathogens can also express their own plasminogen activators, or contain surface proteins that provide binding sites host plasminogen. Plasmin formed under these circumstances also empowers these pathogens to modulate host immune defense mechanisms. Phylogenetic studies have revealed that the plasminogen activating system predates the appearance of fibrin, indicating that plasmin did not evolve as a fibrinolytic protease but perhaps has its roots as an immune modifying protease. While its fibrin removing capacity became apparent in lower vertebrates these primitive under-appreciated immune modifying functions still remain and are now becoming more recognised.

scholarly journals ACTN4 Mediates SEPT14 Mutation-Induced Sperm Head Defects

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 518
Author(s):  
Yu-Hua Lin ◽  
Chia-Yen Huang ◽  
Chih-Chun Ke ◽  
Ya-Yun Wang ◽  
Tsung-Hsuan Lai ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cell Model ◽  
Membrane Dynamics ◽  
Sperm Head ◽  
Cellular Processes ◽  
Germ Cell Line ◽  
Head Formation ◽  
Fourth Component ◽  
Related Proteins ◽  
Cellular Components

Septins (SEPTs) are highly conserved GTP-binding proteins and the fourth component of the cytoskeleton. Polymerized SEPTs participate in the modulation of various cellular processes, such as cytokinesis, cell polarity, and membrane dynamics, through their interactions with microtubules, actin, and other cellular components. The main objective of this study was to dissect the molecular pathological mechanism of SEPT14 mutation-induced sperm head defects. To identify SEPT14 interactors, co-immunoprecipitation (co-IP) and nano-liquid chromatography-mass spectrometry/mass spectrometry were applied. Immunostaining showed that SEPT14 was significantly localized to the manchette structure. The SEPT14 interactors were identified and classified as (1) SEPT-, (2) microtubule-, (3) actin-, and (4) sperm structure-related proteins. One interactor, ACTN4, an actin-holding protein, was selected for further study. Co-IP experiments showed that SEPT14 interacts with ACTN4 in a male germ cell line. SEPT14 also co-localized with ACTN4 in the perinuclear and manchette regions of the sperm head in early elongating spermatids. In the cell model, mutated SEPT14 disturbed the localization pattern of ACTN4. In a clinical aspect, sperm with mutant SEPT14, SEPT14A123T (p.Ala123Thr), and SEPT14I333T (p.Ile333Thr), have mislocalized and fragmented ACTN4 signals. Sperm head defects in donors with SEPT14 mutations are caused by disruption of the functions of ACTN4 and actin during sperm head formation.

Immunotherapy of Chemically-Induced Tumors in the Hamster Cheek Pouch with Dinitrochlorobenzene

1978 ◽  
Vol 57 (4) ◽  
pp. 625-630 ◽  
Author(s):  
Martin Marshack ◽  
Patrick Toto ◽  
Ronald Kerman
Keyword(s):  
Defense Mechanisms ◽  
Immune Defense ◽  
Lymphoid Cells ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Time Intervals ◽  
Tumor Induction ◽  
Chemically Induced ◽  
Induced Tumors ◽  
Tumor Area

Immune stimulation with an agent such as dinitrochlorobenzene (DNCB) may delay chemcal carcinogenesis. Dimethylbenzanthracene (DMBA) was used to chemically induce tumors in the hamster buccal pouch. Hamsters were studied for the effect of DNCB sensitization in the buccal pouch prior to or after DMBA tumor induction. At appropriate time intervals the hamsters were sacrificed and each cheek pouch was examined histologically for the development of DMBA-induced tumors and for the presence of lymphoid cells infiltrating the tumor site. The results show that DNCB immunotherapy or immunoprophylaxis prior to or following DMBA tumor induction can alter the type of tumor produced and stimulate an infiltration of lymphoid cells into the tumor area probably invoking immune defense mechanisms.

scholarly journals Cooperative Immune Suppression by Escherichia coli and Shigella Effector Proteins

2018 ◽  
Vol 86 (4) ◽  
Author(s):  
Maarten F. de Jong ◽  
Neal M. Alto
Keyword(s):  
Escherichia Coli ◽  
Defense Mechanisms ◽  
Immune Defense ◽  
Effector Proteins ◽  
Innate Immune ◽  
Host Cells ◽  
Secretion Systems ◽  
Content Type ◽  
E Coli ◽  
Type Iii Secretion Systems

ABSTRACT The enteric attaching and effacing (A/E) pathogens enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) and the invasive pathogens enteroinvasive E. coli (EIEC) and Shigella encode type III secretion systems (T3SS) used to inject effector proteins into human host cells during infection. Among these are a group of effectors required for NF-κB-mediated host immune evasion. Recent studies have identified several effector proteins from A/E pathogens and EIEC/ Shigella that are involved in suppression of NF-κB and have uncovered their cellular and molecular functions. A novel mechanism among these effectors from both groups of pathogens is to coordinate effector function during infection. This cooperativity among effector proteins explains how bacterial pathogens are able to effectively suppress innate immune defense mechanisms in response to diverse classes of immune receptor signaling complexes (RSCs) stimulated during infection.

scholarly journals Preterm birth and sustained inflammation: consequences for the neonate

2020 ◽  
Vol 42 (4) ◽  
pp. 451-468 ◽  
Author(s):  
Alexander Humberg ◽  
◽  
Ingmar Fortmann ◽  
Bastian Siller ◽  
Matthias Volkmar Kopp ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Preterm Infants ◽  
Defense Mechanisms ◽  
Preterm Births ◽  
Immune Defense ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Organ Systems ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Abstract Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes with or without chorioamnionitis (“first inflammatory hit”). Preterm babies have highly vulnerable body surfaces and immature organ systems. They are postnatally confronted with a drastically altered antigen exposure including hospital-specific microbes, artificial devices, drugs, nutritional antigens, and hypoxia or hyperoxia (“second inflammatory hit”). This is of particular importance to extremely preterm infants born before 28 weeks, as they have not experienced important “third-trimester” adaptation processes to tolerate maternal and self-antigens. Instead of a balanced adaptation to extrauterine life, the delicate co-regulation between immune defense mechanisms and immunosuppression (tolerance) to allow microbiome establishment is therefore often disturbed. Hence, preterm infants are predisposed to sepsis but also to several injurious conditions that can contribute to the onset or perpetuation of sustained inflammation (SI). This is a continuing challenge to clinicians involved in the care of preterm infants, as SI is regarded as a crucial mediator for mortality and the development of morbidities in preterm infants. This review will outline the (i) role of inflammation for short-term consequences of preterm birth and (ii) the effect of SI on organ development and long-term outcome.

scholarly journals About the dangers, costs and benefits of living an aerobic lifestyle

2014 ◽  
Vol 42 (4) ◽  
pp. 917-921 ◽  
Author(s):  
Daniela Knoefler ◽  
Lars I.O. Leichert ◽  
Maike Thamsen ◽  
Claudia M. Cremers ◽  
Dana Reichmann ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Research Programme ◽  
Future Research ◽  
Mammalian Host ◽  
Costs And Benefits ◽  
Cellular Processes ◽  
Effective Antioxidant ◽  
Development And Differentiation ◽  
Micro Organisms

The era in which ROS (reactive oxygen species) were simply the ‘bad boys of biology’ is clearly over. High levels of ROS are still rightfully considered to be toxic to many cellular processes and, as such, contribute to disease conditions and cell death. However, the high toxicity of ROS is also extremely beneficial, particularly as it is used to kill invading micro-organisms during mammalian host defence. Moreover, a transient, often more localized, increase in ROS levels appears to play a major role in signal transduction processes and positively affects cell growth, development and differentiation. At the heart of all these processes are redox-regulated proteins, which use oxidation-sensitive cysteine residues to control their function and by extension the function of the pathways that they are part of. Our work has contributed to changing the view about ROS through: (i) our characterization of Hsp33 (heat-shock protein 33), one of the first redox-regulated proteins identified, whose function is specifically activated by ROS, (ii) the development of quantitative tools that reveal extensive redox-sensitive processes in bacteria and eukaryotes, and (iii) the discovery of a link between early exposure to oxidants and aging. Our future research programme aims to generate an integrated and system-wide view of the beneficial and deleterious effects of ROS with the central goal to develop more effective antioxidant strategies and more powerful antimicrobial agents.

scholarly journals Columbia spotted frogs (Rana luteiventris) have characteristic skin microbiota that may be shaped by cutaneous skin peptides and the environment

2020 ◽  
Vol 96 (10) ◽  
Author(s):  
A H Loudon ◽  
A Kurtz ◽  
E Esposito ◽  
T P Umile ◽  
K P C Minbiole ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Batrachochytrium Dendrobatidis ◽  
Skin Diseases ◽  
Environmental Influence ◽  
Bacterial Community Composition ◽  
Amphibian Declines ◽  
Immune Defense ◽  
Rana Luteiventris ◽  
Skin Bacteria ◽  
Metabolite Profiles

ABSTRACT Global amphibian declines due to the fungal pathogen Batrachochytrium dendrobatidis (Bd) have led to questions about how amphibians defend themselves against skin diseases. A total of two amphibian defense mechanisms are antimicrobial peptides (AMPs), a component of amphibian innate immune defense and symbiotic skin bacteria, which can act in synergy. We characterized components of these factors in four populations of Columbia spotted frogs (Rana luteiventris) to investigate their role in disease defense. We surveyed the ability of their AMPs to inhibit Bd, skin bacterial community composition, skin metabolite profiles and presence and intensity of Bd infection. We found that AMPs from R. luteiventris inhibited Bd in bioassays, but inhibition did not correlate with Bd intensity on frogs. R. luteiventris had two prevalent and abundant core bacteria: Rhizobacter and Chryseobacterium. Rhizobacter relative abundance was negatively correlated with AMP's ability to inhibit Bd, but was not associated with Bd status itself. There was no relationship between metabolites and Bd. Bacterial communities and Bd differ by location, which suggests a strong environmental influence. R. luteiventris are dominated by consistent core bacteria, but also house transient bacteria that are site specific. Our emergent hypothesis is that host control and environmental factors shape the microbiota on R. luteiventris.

scholarly journals Differential Proteomics Reveals miR-155 as a Novel Indicator of Liver and Spleen Pathology in the Symptomatic Niemann-Pick Disease, Type C1 Mouse Model

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 994 ◽  
Author(s):  
Melissa Pergande ◽  
Antony Cougnoux ◽  
Rathnayake Rathnayake ◽  
Forbes Porter ◽  
Stephanie Cologna
Keyword(s):  
Disease Type ◽  
Phosphoinositide Metabolism ◽  
Differential Proteomics ◽  
Protein Targets ◽  
Cellular Processes ◽  
Niemann Pick Disease ◽  
Lysosomal System ◽  
Niemann Pick ◽  
Lipid Storage Disorder ◽  
Pick Disease

Niemann-Pick disease, type C1 (NPC1) is a rare, autosomal recessive, lipid storage disorder caused by mutations in NPC1. As a result, there is accumulation of unesterified cholesterol and sphingolipids in the late endosomal/lysosomal system. Clinically, patients can present with splenomegaly and hepatomegaly. In the current study, we analyzed the differential proteome of the spleen in symptomatic Npc1−/− mice to complement previous studies focused on the differential proteome of the liver, and then evaluated biomolecules that may serve as tissue biomarkers. The proteomic analysis revealed altered pathways in NPC1 representing different functional categories including heme synthesis, cellular regulation and phosphoinositide metabolism in both tissues. Differential proteins included several activators of the ubiquitous and critical protein, Akt, a major kinase involved in multiple cellular processes. Evaluation of Akt revealed decreased expression in both the liver and spleen tissues of symptomatic Npc1−/− mice. Upstream regulation analysis also suggested that miR-155 may modulate the differences of known downstream protein targets observed in our dataset. Upon evaluation of miR-155, we observed an increased expression in the liver and decreased expression in the spleen of symptomatic Npc1−/− mice. Here, we propose that miR-155 may be a novel indicator of spleen and liver pathology in NPC1.

scholarly journals Role of Opsonophagocytosis in Immune Protection against Malaria

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 264
Author(s):  
Wolfgang W. Leitner ◽  
Megan Haraway ◽  
Tony Pierson ◽  
Elke S. Bergmann-Leitner
Keyword(s):  
Protective Immunity ◽  
Defense Mechanisms ◽  
Vaccine Development ◽  
Immune Defense ◽  
Complement Components ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Antibody Titers ◽  
Simple Measurement ◽  
Humoral Responses

The quest for immune correlates of protection continues to slow vaccine development. To date, only vaccine-induced antibodies have been confirmed as direct immune correlates of protection against a plethora of pathogens. Vaccine immunologists, however, have learned through extensive characterizations of humoral responses that the quantitative assessment of antibody responses alone often fails to correlate with protective immunity or vaccine efficacy. Despite these limitations, the simple measurement of post-vaccination antibody titers remains the most widely used approaches for vaccine evaluation. Developing and performing functional assays to assess the biological activity of pathogen-specific responses continues to gain momentum; integrating serological assessments with functional data will ultimately result in the identification of mechanisms that contribute to protective immunity and will guide vaccine development. One of these functional readouts is phagocytosis of antigenic material tagged by immune molecules such as antibodies and/or complement components. This review summarizes our current understanding of how phagocytosis contributes to immune defense against pathogens, the pathways involved, and defense mechanisms that pathogens have evolved to deal with the threat of phagocytic removal and destruction of pathogens.

Sign in / Sign up

Export Citation Format

Share Document