scholarly journals Intracellular Pathogens: Host Immunity and Microbial Persistence Strategies

2019 ◽  
Vol 2019 ◽  
pp. 1-24 ◽  
Author(s):  
Aneesh Thakur ◽  
Heidi Mikkelsen ◽  
Gregers Jungersen
Keyword(s):  
Infectious Diseases ◽  
Immune Escape ◽  
Host Immunity ◽  
Host Cells ◽  
World Health ◽  
Host Immune System ◽  
Intracellular Pathogens ◽  
Diverse Range ◽  
Effector Functions ◽  
Persistence Strategies

Infectious diseases caused by pathogens including viruses, bacteria, fungi, and parasites are ranked as the second leading cause of death worldwide by the World Health Organization. Despite tremendous improvements in global public health since 1950, a number of challenges remain to either prevent or eradicate infectious diseases. Many pathogens can cause acute infections that are effectively cleared by the host immunity, but a subcategory of these pathogens called “intracellular pathogens” can establish persistent and sometimes lifelong infections. Several of these intracellular pathogens manage to evade the host immune monitoring and cause disease by replicating inside the host cells. These pathogens have evolved diverse immune escape strategies and overcome immune responses by residing and multiplying inside host immune cells, primarily macrophages. While these intracellular pathogens that cause persistent infections are phylogenetically diverse and engage in diverse immune evasion and persistence strategies, they share common pathogen type-specific mechanisms during host-pathogen interaction inside host cells. Likewise, the host immune system is also equipped with a diverse range of effector functions to fight against the establishment of pathogen persistence and subsequent host damage. This article provides an overview of the immune effector functions used by the host to counter pathogens and various persistence strategies used by intracellular pathogens to counter host immunity, which enables their extended period of colonization in the host. The improved understanding of persistent intracellular pathogen-derived infections will contribute to develop improved disease diagnostics, therapeutics, and prophylactics.

scholarly journals Synthesizing within-host and population-level selective pressures on viral populations: the impact of adaptive immunity on viral immune escape

2010 ◽  
Vol 7 (50) ◽  
pp. 1311-1318 ◽  
Author(s):  
Igor Volkov ◽  
Kim M. Pepin ◽  
James O. Lloyd-Smith ◽  
Jayanth R. Banavar ◽  
Bryan T. Grenfell
Keyword(s):  
Evolutionary Dynamics ◽  
Immune Escape ◽  
Adaptive Immune Response ◽  
Population Level ◽  
Analytical Framework ◽  
Host Population ◽  
Host Immunity ◽  
Host Cells ◽  
Susceptible Host ◽  
The Impact

The evolution of viruses to escape prevailing host immunity involves selection at multiple integrative scales, from within-host viral and immune kinetics to the host population level. In order to understand how viral immune escape occurs, we develop an analytical framework that links the dynamical nature of immunity and viral variation across these scales. Our epidemiological model incorporates within-host viral evolutionary dynamics for a virus that causes acute infections (e.g. influenza and norovirus) with changes in host immunity in response to genetic changes in the virus population. We use a deterministic description of the within-host replication dynamics of the virus, the pool of susceptible host cells and the host adaptive immune response. We find that viral immune escape is most effective at intermediate values of immune strength. At very low levels of immunity, selection is too weak to drive immune escape in recovered hosts, while very high levels of immunity impose such strong selection that viral subpopulations go extinct before acquiring enough genetic diversity to escape host immunity. This result echoes the predictions of simpler models, but our formulation allows us to dissect the combination of within-host and transmission-level processes that drive immune escape.

scholarly journals Prison Break: Pathogens' Strategies To Egress from Host Cells

2012 ◽  
Vol 76 (4) ◽  
pp. 707-720 ◽  
Author(s):  
Nikolas Friedrich ◽  
Monica Hagedorn ◽  
Dominique Soldati-Favre ◽  
Thierry Soldati
Keyword(s):  
Host Cell ◽  
Pathogenic Bacteria ◽  
Wide Spectrum ◽  
Host Cells ◽  
Host Immune System ◽  
Intracellular Pathogens ◽  
Pathogenic Yeast ◽  
Apicomplexan Parasites ◽  
Strategic Process ◽  
Intimate Association

SUMMARYA wide spectrum of pathogenic bacteria and protozoa has adapted to an intracellular life-style, which presents several advantages, including accessibility to host cell metabolites and protection from the host immune system. Intracellular pathogens have developed strategies to enter and exit their host cells while optimizing survival and replication, progression through the life cycle, and transmission. Over the last decades, research has focused primarily on entry, while the exit process has suffered from neglect. However, pathogen exit is of fundamental importance because of its intimate association with dissemination, transmission, and inflammation. Hence, to fully understand virulence mechanisms of intracellular pathogens at cellular and systemic levels, it is essential to consider exit mechanisms to be a key step in infection. Exit from the host cell was initially viewed as a passive process, driven mainly by physical stress as a consequence of the explosive replication of the pathogen. It is now recognized as a complex, strategic process termed “egress,” which is just as well orchestrated and temporally defined as entry into the host and relies on a dynamic interplay between host and pathogen factors. This review compares egress strategies of bacteria, pathogenic yeast, and kinetoplastid and apicomplexan parasites. Emphasis is given to recent advances in the biology of egress in mycobacteria and apicomplexans.

scholarly journals The Mechanism of Facultative Intracellular Parasitism of Brucella

2021 ◽  
Vol 22 (7) ◽  
pp. 3673
Author(s):  
Hanwei Jiao ◽  
Zhixiong Zhou ◽  
Bowen Li ◽  
Yu Xiao ◽  
Mengjuan Li ◽  
...  
Keyword(s):  
Persistent Infection ◽  
Theoretical Basis ◽  
Immune Escape ◽  
Animal Husbandry ◽  
Bactericidal Effect ◽  
Host Cells ◽  
Host Immune System ◽  
Treatment And Prevention ◽  
Long Time ◽  
Immune Escape Mechanisms

Brucellosis is a highly prevalent zoonotic disease characterized by abortion and reproductive dysfunction in pregnant animals. Although the mortality rate of Brucellosis is low, it is harmful to human health, and also seriously affects the development of animal husbandry, tourism and international trade. Brucellosis is caused by Brucella, which is a facultative intracellular parasitic bacteria. It mainly forms Brucella-containing vacuoles (BCV) in the host cell to avoid the combination with lysosome (Lys), so as to avoid the elimination of it by the host immune system. Brucella not only has the ability to resist the phagocytic bactericidal effect, but also can make the host cells form a microenvironment which is conducive to its survival, reproduction and replication, and survive in the host cells for a long time, which eventually leads to the formation of chronic persistent infection. Brucella can proliferate and replicate in cells, evade host immune response and induce persistent infection, which are difficult problems in the treatment and prevention of Brucellosis. Therefore, the paper provides a preliminary overview of the facultative intracellular parasitic and immune escape mechanisms of Brucella, which provides a theoretical basis for the later study on the pathogenesis of Brucella.

scholarly journals Manipulation of Rab GTPase Function by Intracellular Bacterial Pathogens

2007 ◽  
Vol 71 (4) ◽  
pp. 636-652 ◽  
Author(s):  
John H. Brumell ◽  
Marci A. Scidmore
Keyword(s):  
Host Cell ◽  
Bacterial Pathogens ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Rab Gtpase ◽  
Host Immune System ◽  
Intracellular Pathogens ◽  
Cell Trafficking ◽  
Rab Gtpases

SUMMARY Intracellular bacterial pathogens have evolved highly specialized mechanisms to enter and survive within their eukaryotic hosts. In order to do this, bacterial pathogens need to avoid host cell degradation and obtain nutrients and biosynthetic precursors, as well as evade detection by the host immune system. To create an intracellular niche that is favorable for replication, some intracellular pathogens inhibit the maturation of the phagosome or exit the endocytic pathway by modifying the identity of their phagosome through the exploitation of host cell trafficking pathways. In eukaryotic cells, organelle identity is determined, in part, by the composition of active Rab GTPases on the membranes of each organelle. This review describes our current understanding of how selected bacterial pathogens regulate host trafficking pathways by the selective inclusion or retention of Rab GTPases on membranes of the vacuoles that they occupy in host cells during infection.

Organization of restrictive quarantine measures to prevent especially dangerous infections

2020 ◽  
pp. 6-11
Author(s):  
Petr Ilyin
Keyword(s):  
Infectious Diseases ◽  
Clinical Symptoms ◽  
International Health ◽  
World Health ◽  
The World ◽  
History Of ◽  
Entire History ◽  
Health Organization ◽  
Former Ussr ◽  
Health Regulations

Especially dangerous infections (EDIs) belong to the conditionally labelled group of infectious diseases that pose an exceptional epidemic threat. They are highly contagious, rapidly spreading and capable of affecting wide sections of the population in the shortest possible time, they are characterized by the severity of clinical symptoms and high mortality rates. At the present stage, the term "especially dangerous infections" is used only in the territory of the countries of the former USSR, all over the world this concept is defined as "infectious diseases that pose an extreme threat to public health on an international scale." Over the entire history of human development, more people have died as a result of epidemics and pandemics than in all wars combined. The list of especially dangerous infections and measures to prevent their spread were fixed in the International Health Regulations (IHR), adopted at the 22nd session of the WHO's World Health Assembly on July 26, 1969. In 1970, at the 23rd session of the WHO's Assembly, typhus and relapsing fever were excluded from the list of quarantine infections. As amended in 1981, the list included only three diseases represented by plague, cholera and anthrax. However, now annual additions of new infections endemic to different parts of the earth to this list take place. To date, the World Health Organization (WHO) has already included more than 100 diseases in the list of especially dangerous infections.

Drinking-Water Quality and Intestinal Infectious Diseases in a Colombian Department, 2010-2016

2020 ◽  
pp. 21-29
Author(s):  
Dora Cardona Rivas ◽  
Militza Yulain Cardona Guzmán ◽  
Olga Lucía Ocampo López
Keyword(s):  
Water Quality ◽  
Drinking Water ◽  
Infectious Diseases ◽  
Disease Burden ◽  
Social Protection ◽  
Drinking Water Quality ◽  
World Health ◽  
The Social ◽  
Etiological Agents ◽  
Health Organization

Objective: To characterize the burden of intestinal infectious diseases attributable to drinking-water quality in 27 municipalities in the central region of Colombia. Materials and methods: A time-trend ecological study. The drinking-water quality of the National Institute of Health and the Institute of Hydrology, Meteorology and Environmental Studies was identified. The disease burden was calculated based on the mortality registered in the National Department of Statistics and the records of morbidity attended by the Social Protection Integrated Information System. The etiological agents reported in morbidity records and the observation of environmental conditions in the municipalities of the study were included. The disease burden was determined according to the methodology recommended by the World Health Organization (WHO).

scholarly journals The novel Dbl homology/BAR domain protein, MsgA, of Talaromyces marneffei regulates yeast morphogenesis during growth inside host cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Harshini Weerasinghe ◽  
Hayley E. Bugeja ◽  
Alex Andrianopoulos
Keyword(s):  
Pathogenic Fungi ◽  
Host Cells ◽  
Microbial Pathogens ◽  
Mammalian Host ◽  
Host Immune System ◽  
Nucleotide Exchange ◽  
Phagocytic Cells ◽  
Macrophage Infection ◽  
Bar Domain ◽  
Talaromyces Marneffei

AbstractMicrobial pathogens have evolved many strategies to evade recognition by the host immune system, including the use of phagocytic cells as a niche within which to proliferate. Dimorphic pathogenic fungi employ an induced morphogenetic transition, switching from multicellular hyphae to unicellular yeast that are more compatible with intracellular growth. A switch to mammalian host body temperature (37 °C) is a key trigger for the dimorphic switch. This study describes a novel gene, msgA, from the dimorphic fungal pathogen Talaromyces marneffei that controls cell morphology in response to host cues rather than temperature. The msgA gene is upregulated during murine macrophage infection, and deletion results in aberrant yeast morphology solely during growth inside macrophages. MsgA contains a Dbl homology domain, and a Bin, Amphiphysin, Rvs (BAR) domain instead of a Plekstrin homology domain typically associated with guanine nucleotide exchange factors (GEFs). The BAR domain is crucial in maintaining yeast morphology and cellular localisation during infection. The data suggests that MsgA does not act as a canonical GEF during macrophage infection and identifies a temperature independent pathway in T. marneffei that controls intracellular yeast morphogenesis.

scholarly journals Evolutionary Genetics of Mycobacterium tuberculosis and HIV-1: “The Tortoise and the Hare”

2021 ◽  
Vol 9 (1) ◽  
pp. 147
Author(s):  
Ana Santos-Pereira ◽  
Carlos Magalhães ◽  
Pedro M. M. Araújo ◽  
Nuno S. Osório
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Evolutionary Dynamics ◽  
Evolutionary Genetics ◽  
Host Cells ◽  
Whole Genome Sequencing Data ◽  
Host Immune System ◽  
Viral Mutant ◽  
Hiv 1

The already enormous burden caused by Mycobacterium tuberculosis and Human Immunodeficiency Virus type 1 (HIV-1) alone is aggravated by co-infection. Despite obvious differences in the rate of evolution comparing these two human pathogens, genetic diversity plays an important role in the success of both. The extreme evolutionary dynamics of HIV-1 is in the basis of a robust capacity to evade immune responses, to generate drug-resistance and to diversify the population-level reservoir of M group viral subtypes. Compared to HIV-1 and other retroviruses, M. tuberculosis generates minute levels of genetic diversity within the host. However, emerging whole-genome sequencing data show that the M. tuberculosis complex contains at least nine human-adapted phylogenetic lineages. This level of genetic diversity results in differences in M. tuberculosis interactions with the host immune system, virulence and drug resistance propensity. In co-infected individuals, HIV-1 and M. tuberculosis are likely to co-colonize host cells. However, the evolutionary impact of the interaction between the host, the slowly evolving M. tuberculosis bacteria and the HIV-1 viral “mutant cloud” is poorly understood. These evolutionary dynamics, at the cellular niche of monocytes/macrophages, are also discussed and proposed as a relevant future research topic in the context of single-cell sequencing.

scholarly journals Host-Pathogen Adhesion as the Basis of Innovative Diagnostics for Emerging Pathogens

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1259
Author(s):  
Alex van Belkum ◽  
Carina Almeida ◽  
Benjamin Bardiaux ◽  
Sarah V. Barrass ◽  
Sarah J. Butcher ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Receptor Binding ◽  
Pathogen Detection ◽  
Host Cells ◽  
Emerging Pathogens ◽  
Emerging Viruses ◽  
Ligand Interaction ◽  
Novel Structure ◽  
Specificity And Sensitivity

Infectious diseases are an existential health threat, potentiated by emerging and re-emerging viruses and increasing bacterial antibiotic resistance. Targeted treatment of infectious diseases requires precision diagnostics, especially in cases where broad-range therapeutics such as antibiotics fail. There is thus an increasing need for new approaches to develop sensitive and specific in vitro diagnostic (IVD) tests. Basic science and translational research are needed to identify key microbial molecules as diagnostic targets, to identify relevant host counterparts, and to use this knowledge in developing or improving IVD. In this regard, an overlooked feature is the capacity of pathogens to adhere specifically to host cells and tissues. The molecular entities relevant for pathogen–surface interaction are the so-called adhesins. Adhesins vary from protein compounds to (poly-)saccharides or lipid structures that interact with eukaryotic host cell matrix molecules and receptors. Such interactions co-define the specificity and sensitivity of a diagnostic test. Currently, adhesin-receptor binding is typically used in the pre-analytical phase of IVD tests, focusing on pathogen enrichment. Further exploration of adhesin–ligand interaction, supported by present high-throughput “omics” technologies, might stimulate a new generation of broadly applicable pathogen detection and characterization tools. This review describes recent results of novel structure-defining technologies allowing for detailed molecular analysis of adhesins, their receptors and complexes. Since the host ligands evolve slowly, the corresponding adhesin interaction is under selective pressure to maintain a constant receptor binding domain. IVD should exploit such conserved binding sites and, in particular, use the human ligand to enrich the pathogen. We provide an inventory of methods based on adhesion factors and pathogen attachment mechanisms, which can also be of relevance to currently emerging pathogens, including SARS-CoV-2, the causative agent of COVID-19.

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