scholarly journals Plasmodium berghei-Released Factor, PbTIP, Modulates the Host Innate Immune Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Inderjeet Kalia ◽  
Rajesh Anand ◽  
Afshana Quadiri ◽  
Shreya Bhattacharya ◽  
Bijayalaxmi Sahoo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Plasmodium Berghei ◽  
Immune Surveillance ◽  
Hypothetical Protein ◽  
Disease Diagnosis ◽  
Host Responses ◽  
Gene Transcript ◽  
Host Immune Responses ◽  
Human T Cell ◽  
Successful Infection

The Plasmodium parasite has to cross various immunological barriers for successful infection. Parasites have evolved mechanisms to evade host immune responses, which hugely contributes to the successful infection and transmission by parasites. One way in which a parasite evades immune surveillance is by expressing molecular mimics of the host molecules in order to manipulate the host responses. In this study, we report a Plasmodium berghei hypothetical protein, PbTIP (PbANKA_124360.0), which is a Plasmodium homolog of the human T-cell immunomodulatory protein (TIP). The latter possesses immunomodulatory activities and suppressed the host immune responses in a mouse acute graft-versus-host disease (GvHD) model. The Plasmodium berghei protein, PbTIP, is expressed on the merozoite surface and exported to the host erythrocyte surface upon infection. It is shed in the blood circulation by the activity of an uncharacterized membrane protease(s). The shed PbTIP could be detected in the host serum during infection. Our results demonstrate that the shed PbTIP exhibits binding on the surface of macrophages and reduces their inflammatory cytokine response while upregulating the anti-inflammatory cytokines such as TGF-β and IL-10. Such manipulated immune responses are observed in the later stage of malaria infection. PbTIP induced Th2-type gene transcript changes in macrophages, hinting toward its potential to regulate the host immune responses against the parasite. Therefore, this study highlights the role of a Plasmodium-released protein, PbTIP, in immune evasion using macrophages, which may represent the critical strategy of the parasite to successfully survive and thrive in its host. This study also indicates the human malaria parasite TIP as a potential diagnostic molecule that could be exploited in lateral flow-based immunochromatographic tests for malaria disease diagnosis.

scholarly journals Fighting the Monster: Applying the Host Damage Framework to Human Central Nervous System Infections

mBio ◽  
2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Anil A. Panackal ◽  
Kim C. Williamson ◽  
Diederik van de Beek ◽  
David R. Boulware ◽  
Peter R. Williamson
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Responses ◽  
Host Responses ◽  
Microbial Pathogenesis ◽  
Central Nervous System Infections ◽  
Human Central Nervous System ◽  
Host Immune Responses ◽  
Immune Mediated ◽  
Damage Response

ABSTRACTThe host damage-response framework states that microbial pathogenesis is a product of microbial virulence factors and collateral damage from host immune responses. Immune-mediated host damage is particularly important within the size-restricted central nervous system (CNS), where immune responses may exacerbate cerebral edema and neurological damage, leading to coma and death. In this review, we compare human host and therapeutic responses in representative nonviral generalized CNS infections that induce archetypal host damage responses: cryptococcal menigoencephalitis and tuberculous meningitis in HIV-infected and non-HIV-infected patients, pneumococcal meningitis, and cerebral malaria. Consideration of the underlying patterns of host responses provides critical insights into host damage and may suggest tailored adjunctive therapeutics to improve disease outcome.

scholarly journals A model symbiosis reveals a role for sheathed-flagellum rotation in the release of immunogenic lipopolysaccharide

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Caitlin A Brennan ◽  
Jason R Hunt ◽  
Natacha Kremer ◽  
Benjamin C Krasity ◽  
Michael A Apicella ◽  
...  
Keyword(s):  
Immune Responses ◽  
Unknown Function ◽  
Vibrio Fischeri ◽  
Host Responses ◽  
Tissue Tropism ◽  
Human Pathogens ◽  
Bacterial Flagella ◽  
Host Immune Responses ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Bacterial flagella mediate host–microbe interactions through tissue tropism during colonization, as well as by activating immune responses. The flagellar shaft of some bacteria, including several human pathogens, is encased in a membranous sheath of unknown function. While it has been hypothesized that the sheath may allow these bacteria to evade host responses to the immunogenic flagellin subunit, this unusual structural feature has remained an enigma. Here we demonstrate that the rotation of the sheathed flagellum in both the mutualist Vibrio fischeri and the pathogen Vibrio cholerae promotes release of a potent bacteria-derived immunogen, lipopolysaccharide, found in the flagellar sheath. We further present a new role for the flagellar sheath in triggering, rather than circumventing, host immune responses in the model squid-vibrio symbiosis. Such an observation not only has implications for the study of bacterial pathogens with sheathed flagella, but also raises important biophysical questions of sheathed-flagellum function.

scholarly journals Host immune responses to enzootic and invasive pathogen lineages vary in magnitude, timing, and efficacy

2021 ◽  
Author(s):  
Coby A McDonald ◽  
C. Guilherme Becker ◽  
Carolina Lambertini ◽  
Luis Felipe Toledo ◽  
Celio FB Haddad ◽  
...  
Keyword(s):  
Immune Responses ◽  
Late Stage ◽  
Infection Intensity ◽  
Differentially Expressed ◽  
Host Responses ◽  
Host Immune Responses ◽  
Network Analyses ◽  
Stage Disease ◽  
Late Stage Disease ◽  
Stage Infection

Infectious diseases of wildlife continue to pose a threat to biodiversity worldwide, yet pathogens are far from monolithic in virulence. Within the same pathogen species, virulence can vary considerably depending on strain or lineage, in turn eliciting variable host responses. One pathogen that has caused extensive biodiversity loss is the amphibian-killing fungus, Batrachochytrium dendrobatidis (Bd), which is comprised of a globally widespread hypervirulent lineage (Bd-GPL), and multiple geographically restricted lineages. Whereas host immunogenomic responses to Bd-GPL have been characterized in a number of amphibian species, immunogenomic responses to geographically-restricted, enzootic Bd lineages are unknown. To examine lineage-specific host immune responses to Bd, we exposed a species of pumpkin toadlet, Brachycephalus pitanga, which is endemic to Brazil's Southern Atlantic Forest, to either the Bd-GPL or the enzootic Bd-Asia-2/Brazil (hereafter Bd-Brazil) lineage. We quantified functional immunogenomic responses over the course of infection using differential gene expression tests and coexpression network analyses. Host immune responses varied significantly with Bd lineage. Toadlet responses to Bd-Brazil were weak at early infection (26 genes differentially expressed), peaked by mid-stage infection (435 genes) and were nearly fully resolved by late-stage disease (9 genes). In contrast, responses to Bd-GPL were magnified and delayed; toadlets differentially expressed 97 genes early, 86 genes at mid-stage infection, and 728 genes by late-stage infection. Given that infection intensity did not vary between mid- and late-stage disease, this suggests that pumpkin toadlets may be at least partially tolerant to the geographically-restricted Bd-Brazil lineage. In contrast, mortality was higher in Bd-GPL-infected toadlets, suggesting that late-stage immune activation against Bd-GPL was not protective and was consistent with immune dysregulation previously observed in other species. Our results demonstrate that both the timing of immune response and the particular immune pathways activated are specific to Bd lineage. Within regions where multiple Bd lineages co-occur, and given continued global Bd movement, these differential host responses may influence not only individual disease outcome, but transmission dynamics at the population and community levels.

scholarly journals Genetic Variation/Evolution and Differential Host Responses Resulting from In-Patient Adaptation ofMycobacterium avium

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
N. Kannan ◽  
Y.-P. Lai ◽  
M. Haug ◽  
M. K. Lilleness ◽  
S. S. Bakke ◽  
...  
Keyword(s):  
Immune Responses ◽  
Host Responses ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Differential Host ◽  
Content Type ◽  
Genomic Changes ◽  
Host Immune Responses ◽  
Persistent Infections ◽  
Medical Microbiology

ABSTRACTMembers of theMycobacterium aviumcomplex (MAC) are characterized as nontuberculosis mycobacteria and are pathogenic mainly in immunocompromised individuals. MAC strains show a wide genetic variability, and there is growing evidence suggesting that genetic differences may contribute to a varied immune response that may impact the infection outcome. The current study aimed to characterize the genomic changes withinM.aviumisolates collected from single patients over time and test the host immune responses to these clinical isolates. Pulsed-field gel electrophoresis and whole-genome sequencing were performed on 40 MAC isolates isolated from 15 patients at the Department of Medical Microbiology at St. Olavs Hospital in Trondheim, Norway. Isolates from patients (patients 4, 9, and 13) for whom more than two isolates were available were selected for further analysis. These isolates exhibited extensive sequence variation in the form of single-nucleotide polymorphisms (SNPs), suggesting thatM. aviumaccumulates mutations at higher rates during persistent infections than other mycobacteria. Infection of murine macrophages and mice with sequential isolates from patients showed a tendency toward increased persistence and the downregulation of inflammatory cytokines by host-adaptedM. aviumstrains. The study revealed the rapid genetic evolution ofM. aviumin chronically infected patients, accompanied by changes in the virulence properties of the sequential mycobacterial isolates.

scholarly journals Pathogenicity, Host Responses and Implications for Management of EnterohemorrhagicEscherichia coliO157:H7 Infection

2013 ◽  
Vol 27 (5) ◽  
pp. 281-285 ◽  
Author(s):  
Nathan K Ho ◽  
Aleah C Henry ◽  
Kathene Johnson-Henry ◽  
Philip M Sherman
Keyword(s):  
Escherichia Coli ◽  
Immune Responses ◽  
Host Responses ◽  
Significant Morbidity ◽  
Shiga Toxins ◽  
Waterborne Pathogen ◽  
Host Immune Responses ◽  
Industrialized Nations ◽  
Enterocyte Effacement ◽  
Future Management

EnterohemorrhagicEscherichia coliserotype O157:H7 is a food- and waterborne pathogen that causes significant morbidity and mortality in both developing and industrialized nations. The present review focuses on the history, epidemiology and evolution of the pathogen; provides a mechanistic overview of major virulence factors (including Shiga toxins, locus of enterocyte effacement pathogenicity island and pO157 plasmid); discusses host immune responses to infection; considers available animal models; and provides an overview of current and potential future management considerations.

scholarly journals The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Anthony M. Cadena ◽  
JoAnne L. Flynn ◽  
Sarah M. Fortune
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Clinical Signs ◽  
Host Responses ◽  
Effective Vaccine ◽  
Clear Understanding ◽  
Mycobacterium Tuberculosis Infection ◽  
Major Health ◽  
Host Immune Responses ◽  
Infection Disease

ABSTRACT Tuberculosis remains a major health threat in much of the world. New vaccines against Mycobacterium tuberculosis are essential for preventing infection, disease, and transmission. However, the host immune responses that need to be induced by an effective vaccine remain unclear. Increasingly, it has become clear that early events in infection are of major importance in the eventual outcome of the infection. Studying such events in humans is challenging, as they occur within the lung and thoracic lymph nodes, and any clinical signs of early infection are relatively nonspecific. Nonetheless, clinical studies and animal models of tuberculosis have provided new insights into the local events that occur in the first few weeks of tuberculosis. Development of an effective vaccine requires a clear understanding of the successful (and detrimental) early host responses against M. tuberculosis , with the goal to improve upon natural immune responses and prevent infection or disease.

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