scholarly journals An Update on Host-Pathogen Interplay and Modulation of Immune Responses duringOrientia tsutsugamushiInfection

2018 ◽  
Vol 31 (2) ◽  
Author(s):  
Fabián E. Díaz ◽  
Katia Abarca ◽  
Alexis M. Kalergis
Keyword(s):  
Animal Models ◽  
Immune Responses ◽  
Model Development ◽  
Scientific Progress ◽  
Organ Injury ◽  
Effective Vaccine ◽  
Host Pathogen Interactions ◽  
Content Type ◽  
Recent Advances ◽  
Host Pathogen

SUMMARYThe obligate intracellular bacteriumOrientia tsutsugamushiis the causative agent of scrub typhus in humans, a serious mite-borne disease present in a widespread area of endemicity, which affects an estimated 1 million people every year. This disease may exhibit a broad range of presentations, ranging from asymptomatic to fatal conditions, with the latter being due to disseminated endothelial infection and organ injury. Unique characteristics of the biology and host-pathogen interactions ofO. tsutsugamushi, including the high antigenic diversity among strains and the highly variable, short-lived memory responses developed by the host, underlie difficulties faced in the pursuit of an effective vaccine, which is an imperative need. Other factors that have hindered scientific progress relative to the infectious mechanisms of and the immune response triggered by this bacterium in vertebrate hosts include the limited number of mechanistic studies performed on animal models and the lack of genetic tools currently available for this pathogen. However, recent advances in animal model development are promising to improve our understanding of host-pathogen interactions. Here, we comprehensively discuss the recent advances in and future perspectives on host-pathogen interactions and the modulation of immune responses related to this reemerging disease, highlighting the role of animal models.

scholarly journals MARTX Toxin-Stimulated Interplay between Human Cells and Vibrio vulnificus

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Byoung Sik Kim ◽  
Jong-Hwan Kim ◽  
Sanghyeon Choi ◽  
Shinhye Park ◽  
Eun-Young Lee ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Vibrio Vulnificus ◽  
Expression Profiles ◽  
Host Cells ◽  
Iron Limitation ◽  
Host Pathogen Interactions ◽  
Content Type ◽  
Host Pathogen ◽  
Ht 29

ABSTRACT To understand toxin-stimulated host-pathogen interactions, we performed dual-transcriptome sequencing experiments using human epithelial (HT-29) and differentiated THP-1 (dTHP-1) immune cells infected with the sepsis-causing pathogen Vibrio vulnificus (either the wild-type [WT] pathogen or a multifunctional-autoprocessing repeats-in-toxin [MARTX] toxin-deficient strain). Gene set enrichment analyses revealed MARTX toxin-dependent responses, including negative regulation of extracellular related kinase 1 (ERK1) and ERK2 (ERK1/2) signaling and cell cycle regulation in HT-29 and dTHP-1 cells, respectively. Further analysis of the expression of immune-related genes suggested that the MARTX toxin dampens immune responses in gut epithelial cells but accelerates inflammation and nuclear factor κB (NF-κB) signaling in immune cells. With respect to the pathogen, siderophore biosynthesis genes were significantly more highly expressed in WT V. vulnificus than in the MARTX toxin-deficient mutant upon infection of dTHP-1 cells. Consistent with these results, iron homeostasis genes that limit iron levels for invading pathogens were overexpressed in WT V. vulnificus-infected dTHP-1 cells. Taken together, these results suggest that MARTX toxin regulates host inflammatory responses during V. vulnificus infection while also countering host defense mechanisms such as iron limitation. IMPORTANCE V. vulnificus is an opportunistic human pathogen that can cause life-threatening sepsis in immunocompromised patients via seafood poisoning or wound infection. Among the toxic substances produced by this pathogen, the MARTX toxin greatly contributes to disease progression by promoting the dysfunction and death of host cells, which allows the bacteria to disseminate and colonize the host. In response to this, host cells mount a counterattack against the invaders by upregulating various defense genes. In this study, the gene expression profiles of both host cells and V. vulnificus were analyzed by RNA sequencing to gain a comprehensive understanding of host-pathogen interactions. Our results suggest that V. vulnificus uses the MARTX toxin to subvert host cell immune responses as well as to oppose host counterattacks such as iron limitation.

scholarly journals Giant virus vs amoeba: fight for supremacy

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Graziele Oliveira ◽  
Bernard La Scola ◽  
Jônatas Abrahão
Keyword(s):  
Giant Virus ◽  
Host Pathogen Interactions ◽  
Free Living ◽  
Host Interactions ◽  
Virus Particles ◽  
Recent Advances ◽  
Host Pathogen ◽  
New Hosts ◽  
Giant Viruses

Abstract Since the discovery of mimivirus, numerous giant viruses associated with free-living amoebae have been described. The genome of giant viruses can be more than 2.5 megabases, and virus particles can exceed the size of many bacteria. The unexpected characteristics of these viruses have made them intriguing research targets and, as a result, studies focusing on their interactions with their amoeba host have gained increased attention. Studies have shown that giant viruses can establish host–pathogen interactions, which have not been previously demonstrated, including the unprecedented interaction with a new group of small viruses, called virophages, that parasitize their viral factories. In this brief review, we present recent advances in virophage–giant virus–host interactions and highlight selected studies involving interactions between giant viruses and amoebae. These unprecedented interactions involve the giant viruses mimivirus, marseillevirus, tupanviruses and faustovirus, all of which modulate the amoeba environment, affecting both their replication and their spread to new hosts.

scholarly journals Pseudomonas aeruginosa Contact-Dependent Growth Inhibition Plays Dual Role in Host-Pathogen Interactions

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Jeffrey A. Melvin ◽  
Jordan R. Gaston ◽  
Shawn N. Phillips ◽  
Michael J. Springer ◽  
Christopher W. Marshall ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acute Infection ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Microbial Pathogenesis ◽  
Host Pathogen Interactions ◽  
Gram Negative ◽  
Content Type ◽  
Disease Outcomes ◽  
Host Pathogen

ABSTRACT How bacteria compete and communicate with each other is an increasingly recognized aspect of microbial pathogenesis with a major impact on disease outcomes. Gram-negative bacteria have recently been shown to employ a contact-dependent toxin-antitoxin system to achieve both competition and regulation of their physiology. Here, we show that this system is vital for virulence in acute infection as well as for establishment of chronic infection in the multidrug-resistant pathogen Pseudomonas aeruginosa. Greater understanding of the mechanisms underlying bacterial virulence and infection is important for the development of effective therapeutics in the era of increasing antimicrobial resistance. Microorganisms exist in a diverse ecosystem and have evolved many different mechanisms for sensing and influencing the polymicrobial environment around them, utilizing both diffusible and contact-dependent signals. Contact-dependent growth inhibition (CDI) is one such communication system employed by Gram-negative bacteria. In addition to CDI mediation of growth inhibition, recent studies have demonstrated CDI-mediated control of communal behaviors such as biofilm formation. We postulated that CDI may therefore play an active role in host-pathogen interactions, allowing invading strains to establish themselves at polymicrobial mucosal interfaces through competitive interactions while simultaneously facilitating pathogenic capabilities via CDI-mediated signaling. Here, we show that Pseudomonas aeruginosa produces two CDI systems capable of mediating competition under conditions of growth on a surface or in liquid. Furthermore, we demonstrated a novel role for these systems in contributing to virulence in acute infection models, likely via posttranscriptional regulation of beneficial behaviors. While we did not observe any role for the P. aeruginosa CDI systems in biofilm biogenesis, we did identify for the first time robust CDI-mediated competition during interaction with a mammalian host using a model of chronic respiratory tract infection, as well as evidence that CDI expression is maintained in chronic lung infections. These findings reveal a previously unappreciated role for CDI in host-pathogen interactions and emphasize their importance during infection. IMPORTANCE How bacteria compete and communicate with each other is an increasingly recognized aspect of microbial pathogenesis with a major impact on disease outcomes. Gram-negative bacteria have recently been shown to employ a contact-dependent toxin-antitoxin system to achieve both competition and regulation of their physiology. Here, we show that this system is vital for virulence in acute infection as well as for establishment of chronic infection in the multidrug-resistant pathogen Pseudomonas aeruginosa. Greater understanding of the mechanisms underlying bacterial virulence and infection is important for the development of effective therapeutics in the era of increasing antimicrobial resistance.

scholarly journals Draft Genome Sequences of 12 Monophasic Salmonella enterica subsp. enterica Serotype Typhimurium 1,4,[5],12:i:− Strains Isolated from Wild Griffon Vultures in Eastern Spain

2019 ◽  
Vol 8 (42) ◽  
Author(s):  
Clara Marin ◽  
Giuseppe D’Auria ◽  
Llúcia Martínez-Priego ◽  
Francisco Marco-Jiménez
Keyword(s):  
Salmonella Enterica ◽  
Draft Genome ◽  
Wild Animals ◽  
Genome Sequences ◽  
Host Pathogen Interactions ◽  
Content Type ◽  
Zoonotic Pathogens ◽  
Host Pathogen ◽  
Serovar Typhimurium ◽  
Insight Into

Monophasic Salmonella enterica subsp. enterica serovar Typhimurium is one of the most common zoonotic pathogens. Salmonella species reside in a wide variety of hosts, including wild animals. Thus, we report here the genome sequences of 12 monophasic S. Typhimurium strains isolated from healthy wild vultures to gain better insight into their epidemiology and host-pathogen interactions.

scholarly journals Clinical Candida albicans Vaginal Isolates and a Laboratory Strain Show Divergent Behaviors during Macrophage Interactions

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Franziska Gerwien ◽  
Christine Dunker ◽  
Philipp Brandt ◽  
Enrico Garbe ◽  
Ilse D. Jacobsen ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Fungal Infections ◽  
Laboratory Strain ◽  
Infection Process ◽  
Vulvovaginal Candidiasis ◽  
Host Immune System ◽  
Host Pathogen Interactions ◽  
Content Type ◽  
Host Pathogen

ABSTRACT Typically, established lab strains are widely used to study host-pathogen interactions. However, to better reflect the infection process, the experimental use of clinical isolates has come more into focus. Here, we analyzed the interaction of multiple vaginal isolates of the opportunistic fungal pathogen Candida albicans, the most common cause of vulvovaginal candidiasis in women, with key players of the host immune system: macrophages. We tested several strains isolated from asymptomatic or symptomatic women with acute and recurrent infections. While all clinical strains showed a response similar to the commonly used lab strain SC5314 in various in vitro assays, they displayed remarkable differences during interaction with macrophages. This coincided with significantly reduced β-glucan exposure on the cell surface, which appeared to be a shared property among the tested vaginal strains for yeast extract/peptone/dextrose-grown cells, which is partly lost when the isolates faced vaginal niche-like nutrient conditions. However, macrophage damage, survival of phagocytosis, and filamentation capacities were highly strain-specific. These results highlight the high heterogeneity of C. albicans strains in host-pathogen interactions, which have to be taken into account to bridge the gap between laboratory-gained data and disease-related outcomes in an actual patient. IMPORTANCE Vulvovaginal candidiasis is one of the most common fungal infections in humans with Candida albicans as the major causative agent. This study is the first to compare clinical vaginal isolates of defined patient groups in their interaction with macrophages, highlighting the vastly different outcomes in comparison to a laboratory strain using commonly applied virulence-determining assays.

scholarly journals mSphere of Influence: Clearing a Path for High-Resolution Visualization of Host-Pathogen Interactions In Vivo

mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Shumin Tan
Keyword(s):  
Single Cell ◽  
Dimensional Space ◽  
Whole Body ◽  
Host Pathogen Interactions ◽  
Content Type ◽  
3 Dimensional ◽  
Host Interactions ◽  
Host Pathogen ◽  
Tissue Optical Clearing

ABSTRACT Shumin Tan works in the field of Mycobacterium tuberculosis-host interactions. In this mSphere of Influence article, she reflects on how the paper “Single-cell phenotyping within transparent intact tissue through whole-body clearing” by B. Yang et al. (Cell 158:945–958, 2014, https://doi.org/10.1016/j.cell.2014.07.017) impacted her ideas on approaches to visualize and understand heterogeneous host-pathogen interactions in vivo in 3-dimensional space at the single-cell level, through the tractable and broadly compatible tissue optical clearing methods developed.

scholarly journals Antifungal immune responses: emerging host–pathogen interactions and translational implications

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Vinod Kumar ◽  
Frank L. van de Veerdonk ◽  
Mihai G. Netea
Keyword(s):  
Immune Responses ◽  
Host Pathogen Interactions ◽  
Host Pathogen

Basics of pertussis pathogenesis

Pertussis ◽  
2018 ◽  
pp. 26-41 ◽  
Author(s):  
Amanda L. Skarlupka ◽  
Bodo Linz ◽  
Jennifer Maynard ◽  
Eric T. Harvill
Keyword(s):  
Animal Models ◽  
Adenylate Cyclase ◽  
Pertussis Toxin ◽  
Functional Characterization ◽  
Host Pathogen Interactions ◽  
Host Pathogen ◽  
Complex Picture ◽  
Molecular Components

The use of animal models and in vitro assays has allowed the identification and functional characterization of an iconic set of Bordetella pertussis factors that contribute to its pathogenesis. Much research on B. pertussis has been focused on the effects of pertussis toxin and adenylate cyclase toxin on pathogenesis and disease progression, and on the function of adherence factors. However, much larger sets of factors have been identified and proposed to be involved in host–pathogen interactions, including B. pertussis manipulating the host’s metabolism to its advantage. The identification of a third player, the resident microbiota, reveals a complex picture that has yet to be investigated. The ongoing studies of the molecular components produced by B. pertussis and their effect on the host during infection, commonly referred to as ‘pathogenesis’ research, are crucial to generate understanding of the host–pathogen interactions necessary to design new approaches to prevent and cure disease.

scholarly journals Humoral and Cellular Immune Responses to Yersinia pestis Infection in Long-Term Recovered Plague Patients

2011 ◽  
Vol 19 (2) ◽  
pp. 228-234 ◽  
Author(s):  
Bei Li ◽  
Chunhong Du ◽  
Lei Zhou ◽  
Yujing Bi ◽  
Xiaoyi Wang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Mononuclear Cells ◽  
Vaccine Development ◽  
Effective Vaccine ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Cellular Immune Responses ◽  
Significant Difference ◽  
Cellular Immune

ABSTRACTPlague is one of the most dangerous diseases and is caused byYersinia pestis. Effective vaccine development requires understanding of immune protective mechanisms against the bacterium in humans. In this study, the humoral and memory cellular immune responses in plague patients (n= 65) recovered fromY. pestisinfection during the past 16 years were investigated using a protein microarray and an enzyme-linked immunosorbent spot assay (ELISpot). The seroprevalence to the F1 antigen in all recovered patients is 78.5%. In patients infected more than a decade ago, the antibody-positive rate still remains 69.5%. There is no difference in the antibody presence between gender, age, and infected years, but it seems to be associated with the F1 antibody titers during infection (r= 0.821;P< 0.05). Except F1 antibody, the antibodies against LcrV and YopD were detected in most of the patients, suggesting they could be the potential diagnostic markers for detecting the infection of F1-negative strains. Regarding cellular immunity, the cell number producing gamma interferon (IFN-γ), stimulated by F1 and LcrV, respectively,in vitroto the peripheral blood mononuclear cells of 7 plague patients and 4 negative controls, showed no significant difference, indicating F1 and LcrV are not dominant T cell antigens against plague for a longer time in humans. Our findings have direct implications for the future design and development of effective vaccines againstY. pestisinfection and the development of new target-based diagnostics.

Sign in / Sign up

Export Citation Format

Share Document