scholarly journals Immunologic Pathways in Protective versus Maladaptive Host Responses to Attenuated and Pathogenic Strains ofMycoplasma gallisepticum

2018 ◽  
Vol 87 (3) ◽  
Author(s):  
Jessica Beaudet ◽  
Edan R. Tulman ◽  
Katherine Pflaum ◽  
Jessica A. Canter ◽  
Lawrence K. Silbart ◽  
...  
Keyword(s):  
Innate Immune ◽  
Host Responses ◽  
Immune Gene ◽  
Avian Host ◽  
Innate Immune Responses ◽  
Content Type ◽  
Mucosal Tissues ◽  
Rapid Clearance ◽  
Pathogen Clearance ◽  
Host Genes

ABSTRACTMycoplasmas are small bacterial commensals or pathogens that commonly colonize host mucosal tissues and avoid rapid clearance, in part by stimulating inflammatory, immunopathogenic responses. We previously characterized a wide array of transcriptomic perturbations in avian host tracheal mucosae infected with virulent, immunopathologicMycoplasma gallisepticum; however, mechanisms delineating these from protective responses, such as those induced upon vaccination, have not been thoroughly explored. In this study, host transcriptomic responses to two experimentalM. gallisepticumvaccines were assessed during the first 2 days of infection. Relative to virulent infection, host metabolic and immune gene responses to both vaccines were greatly decreased, including early innate immune responses critical to disease development and subsequent adaptive immunity. These data specify host genes and potential mechanisms contributing to maladaptive versus beneficial host responses—information critical for design of vaccines efficacious in both limiting inflammation and enabling pathogen clearance.

scholarly journals Enterotoxigenic Escherichia coli Prevents Host NF-κB Activation by Targeting IκBα Polyubiquitination

2012 ◽  
Vol 80 (12) ◽  
pp. 4417-4425 ◽  
Author(s):  
Xiaogang Wang ◽  
Philip R. Hardwidge
Keyword(s):  
Escherichia Coli ◽  
Immune Responses ◽  
Diarrheal Disease ◽  
Innate Immune ◽  
Host Cells ◽  
Enterotoxigenic Escherichia Coli ◽  
Host Responses ◽  
Innate Immune Responses ◽  
Content Type ◽  
Heat Stable

ABSTRACTThe NF-κB pathway regulates innate immune responses to infection. NF-κB is activated after pathogen-associated molecular patterns are detected, leading to the induction of proinflammatory host responses. As a countermeasure, bacterial pathogens have evolved mechanisms to subvert NF-κB signaling. EnterotoxigenicEscherichia coli(ETEC) causes diarrheal disease and significant morbidity and mortality for humans in developing nations. The extent to which this important pathogen subverts innate immune responses by directly targeting the NF-κB pathway is an understudied topic. Here we report that ETEC secretes a heat-stable, proteinaceous factor that blocks NF-κB signaling normally induced by tumor necrosis factor (TNF), interleukin-1β, and flagellin. Pretreating intestinal epithelial cells with ETEC supernatant significantly blocked the degradation of the NF-κB inhibitor IκBα without affecting IκBα phosphorylation. Data from immunoprecipitation experiments suggest that the ETEC factor functions by preventing IκBα polyubiquitination. Inhibiting clathrin function blocked the activity of the secreted ETEC factor, suggesting that this yet-uncharacterized activity may utilize clathrin-dependent endocytosis to enter host cells. These data suggest that ETEC evades the host innate immune response by directly modulating NF-κB signaling.

scholarly journals Immunologic Consequences of Hypoxia during Critical Illness

2016 ◽  
Vol 125 (1) ◽  
pp. 237-249 ◽  
Author(s):  
Harmke D. Kiers ◽  
Gert-Jan Scheffer ◽  
Johannes G. van der Hoeven ◽  
Holger K. Eltzschig ◽  
Peter Pickkers ◽  
...  
Keyword(s):  
Immune Responses ◽  
Signaling Pathways ◽  
Daily Practice ◽  
Innate Immune ◽  
Protective Effects ◽  
Innate Immune Responses ◽  
Downstream Signaling ◽  
Pathogen Clearance ◽  
Pharmacologic Modulation ◽  
Oxygen Status

Abstract Hypoxia and immunity are highly intertwined at clinical, cellular, and molecular levels. The prevention of tissue hypoxia and modulation of systemic inflammation are cornerstones of daily practice in the intensive care unit. Potentially, immunologic effects of hypoxia may contribute to outcome and represent possible therapeutic targets. Hypoxia and activation of downstream signaling pathways result in enhanced innate immune responses, aimed to augment pathogen clearance. On the other hand, hypoxia also exerts antiinflammatory and tissue-protective effects in lymphocytes and other tissues. Although human data on the net immunologic effects of hypoxia and pharmacologic modulation of downstream pathways are limited, preclinical data support the concept of tailoring the immune response through modulation of the oxygen status or pharmacologic modulation of hypoxia-signaling pathways in critically ill patients.

scholarly journals Vomocytosis: Too Much Booze, Base, or Calcium?

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Melissa Cruz-Acuña ◽  
Noah Pacifici ◽  
Jamal S. Lewis
Keyword(s):  
Current Knowledge ◽  
Innate Immune ◽  
Macrophage Phenotype ◽  
Innate Immune Responses ◽  
Content Type ◽  
Phagosomal Maturation ◽  
Immunodeficiency Virus ◽  
Cellular Pathways ◽  
The Individual ◽  
Pathogenic Agents

ABSTRACT Macrophages are well known for their phagocytic activity and their role in innate immune responses. Macrophages eat non-self particles, via a variety of mechanisms, and typically break down internalized cargo into small macromolecules. However, some pathogenic agents have the ability to evade this endosomal degradation through a nonlytic exocytosis process termed vomocytosis. This phenomenon has been most often studied for Cryptococcus neoformans, a yeast that causes roughly 180,000 deaths per year, primarily in immunocompromised (e.g., human immunodeficiency virus [HIV]) patients. Existing dogma purports that vomocytosis involves distinctive cellular pathways and intracellular physicochemical cues in the host cell during phagosomal maturation. Moreover, it has been observed that the immunological state of the individual and macrophage phenotype affect vomocytosis outcomes. Here we compile the current knowledge on the factors (with respect to the phagocytic cell) that promote vomocytosis of C. neoformans from macrophages.

scholarly journals Vaccination Route Determines the Kinetics and Magnitude of Nasal Innate Immune Responses in Rainbow Trout (Oncorhynchus mykiss)

Biology ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 319
Author(s):  
Fen Dong ◽  
Luca Tacchi ◽  
Zhen Xu ◽  
Scott E. LaPatra ◽  
Irene Salinas
Keyword(s):  
Rainbow Trout ◽  
Immune Responses ◽  
Survival Rates ◽  
Innate Immune ◽  
Immune Gene ◽  
Innate Immune Responses ◽  
Farmed Fish ◽  
Nasal Vaccination ◽  
Highly Effective ◽  
Response Expression

Many pathogens infect animal hosts via the nasal route. Thus, understanding how vaccination stimulates early nasal immune responses is critical for animal and human health. Vaccination is the most effective method to prevent disease outbreaks in farmed fish. Nasal vaccination induces strong innate and adaptive immune responses in rainbow trout and was shown to be highly effective against infectious hematopoietic necrosis (IHN). However, direct comparisons between intranasal, injection and immersion vaccination routes have not been conducted in any fish species. Moreover, whether injection or immersion routes induce nasal innate immune responses is unknown. The goal of this study is to compare the effects of three different vaccine delivery routes, including intranasal (IN), intramuscular (i.m.) injection and immersion (imm) routes on the trout nasal innate immune response. Expression analyses of 13 immune-related genes in trout nasopharynx-associated lymphoid tissue (NALT), detected significant changes in immune expression in all genes analyzed in response to the three vaccination routes. However, nasal vaccination induced the strongest and fastest changes in innate immune gene expression compared to the other two routes. Challenge experiments 7 days post-vaccination (dpv) show the highest survival rates in the IN- and imm-vaccinated groups. However, survival rates in the imm group were significantly lower than the IN- and i.m.-vaccinated groups 28 dpv. Our results confirm that nasal vaccination of rainbow trout with live attenuated IHNV is highly effective and that the protection conferred by immersion vaccination is transient. These results also demonstrate for the first time that immersion vaccines stimulate NALT immune responses in salmonids.

scholarly journals Remasking of Candida albicans β-Glucan in Response to Environmental pH Is Regulated by Quorum Sensing

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Fabien Cottier ◽  
Sarah Sherrington ◽  
Sarah Cockerill ◽  
Valentina del Olmo Toledo ◽  
Stephen Kissane ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Quorum Sensing ◽  
Immune Responses ◽  
Female Reproductive Tract ◽  
Innate Immune ◽  
Immune Recognition ◽  
Innate Immune Responses ◽  
Content Type ◽  
Cell Wall Remodeling

ABSTRACT Candida albicans is a commensal yeast of the human gut which is tolerated by the immune system but has the potential to become an opportunistic pathogen. One way in which C. albicans achieves this duality is through concealing or exposing cell wall pathogen-associated molecular patterns (PAMPs) in response to host-derived environment cues (pH, hypoxia, and lactate). This cell wall remodeling allows C. albicans to evade or hyperactivate the host’s innate immune responses, leading to disease. Previously, we showed that adaptation of C. albicans to acidic environments, conditions encountered during colonization of the female reproductive tract, induces significant cell wall remodeling resulting in the exposure of two key fungal PAMPs (β-glucan and chitin). Here, we report that this pH-dependent cell wall remodeling is time dependent, with the initial change in pH driving cell wall unmasking, which is then remasked at later time points. Remasking of β-glucan was mediated via the cell density-dependent fungal quorum sensing molecule farnesol, while chitin remasking was mediated via a small, heat-stable, nonproteinaceous secreted molecule(s). Transcript profiling identified a core set of 42 genes significantly regulated by pH over time and identified the transcription factor Efg1 as a regulator of chitin exposure through regulation of CHT2. This dynamic cell wall remodeling influenced innate immune recognition of C. albicans, suggesting that during infection, C. albicans can manipulate the host innate immune responses. IMPORTANCE Candida albicans is part of the microbiota of the skin and gastrointestinal and reproductive tracts of humans and has coevolved with us for millennia. During that period, C. albicans has developed strategies to modulate the host’s innate immune responses, by regulating the exposure of key epitopes on the fungal cell surface. Here, we report that exposing C. albicans to an acidic environment, similar to the one of the stomach or vagina, increases the detection of the yeast by macrophages. However, this effect is transitory, as C. albicans is able to remask these epitopes (glucan and chitin). We found that glucan remasking is controlled by the production of farnesol, a molecule secreted by C. albicans in response to high cell densities. However, chitin-remasking mechanisms remain to be identified. By understanding the relationship between environmental sensing and modulation of the host-pathogen interaction, new opportunities for the development of innovative antifungal strategies are possible.

scholarly journals Activation of NLRP3 and AIM2 Inflammasomes by Porphyromonas gingivalis Infection

2013 ◽  
Vol 82 (1) ◽  
pp. 112-123 ◽  
Author(s):  
Eunjoo Park ◽  
Hee Sam Na ◽  
Yu-Ri Song ◽  
Seong Yeol Shin ◽  
You-Me Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Porphyromonas Gingivalis ◽  
Molecular Mechanisms ◽  
Atp Release ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Innate Immune Responses ◽  
Content Type ◽  
Periodontal Destruction ◽  
Tlr4 Activation

ABSTRACTPorphyromonas gingivalis, a major periodontopathogen, is involved in the pathogenesis of periodontitis. Interleukin-1β (IL-1β), a proinflammatory cytokine, regulates innate immune responses and is critical for the host defense against bacterial infection. However, excessive IL-1β is linked to periodontal destruction. IL-1β synthesis, maturation, and secretion are tightly regulated by Toll-like receptor (TLR) signaling and inflammasome activation. We found much higher levels of inflammasome components in the gingival tissues from patients with chronic periodontitis than in those from healthy controls. To investigate the molecular mechanisms by whichP. gingivalisinfection causes IL-1β secretion, we examined the characteristics ofP. gingivalis-induced signaling in differentiated THP-1 cells. We found thatP. gingivalisinduces IL-1β secretion and inflammatory cell death via caspase-1 activation. We also found thatP. gingivalis-induced IL-1β secretion and pyroptic cell death required both NLRP3 and AIM2 inflammasome activation. The activation of the NLRP3 inflammasome was mediated by ATP release, the P2X7receptor, and lysosomal damage. In addition, we found that the priming signal via TLR2 and TLR4 activation precedesP. gingivalis-induced IL-1β release. Our study provides novel insight into the innate immune response againstP. gingivalisinfection which could potentially be used for the prevention and therapy of periodontitis.

scholarly journals Navigating the Host Cell Response during Entry into Sites of Latent Cytomegalovirus Infection

Pathogens ◽  
2018 ◽  
Vol 7 (1) ◽  
pp. 30 ◽  
Author(s):  
Matthew Murray ◽  
Nicholas Peters ◽  
Matthew Reeves
Keyword(s):  
Viral Infection ◽  
Host Cell ◽  
Innate Immune ◽  
Host Responses ◽  
Hostile Environment ◽  
Innate Immune Responses ◽  
Cellular Functions ◽  
Surface Receptors ◽  
Host Cell Response ◽  
The Impact

The host cell represents a hostile environment that viruses must counter in order to establish infection. Human cytomegalovirus (HCMV) is no different and encodes a multitude of functions aimed at disabling, re-directing or hijacking cellular functions to promulgate infection. However, during the very early stages of infection the virus relies on the outcome of interactions between virion components, cell surface receptors and host signalling pathways to promote an environment that supports infection. In the context of latent infection—where the virus establishes an infection in an absence of many gene products specific for lytic infection—these initial interactions are crucial events. In this review, we will discuss key host responses triggered by viral infection and how, in turn, the virus ameliorates the impact on the establishment of non-lytic infections of cells. We will focus on strategies to evade intrinsic antiviral and innate immune responses and consider their impact on viral infection. Finally, we will consider the hypothesis that the very early events upon viral infection are important for dictating the outcome of infection and consider the possibility that events that occur during entry into non-permissive cells are unique and thus contribute to the establishment of latency.

scholarly journals Flagellin from Recombinant Attenuated Salmonella enterica Serovar Typhimurium Reveals a Fundamental Role in Chicken Innate Immunity

2012 ◽  
Vol 19 (3) ◽  
pp. 304-312 ◽  
Author(s):  
Zhiming Pan ◽  
Qiuxia Cong ◽  
Shizhong Geng ◽  
Qiang Fang ◽  
Xilong Kang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Salmonella Enterica ◽  
Rational Design ◽  
Bacterial Load ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTRecombinant attenuatedSalmonellavaccines have been extensively studied, with a focus on eliciting specific immune responses against foreign antigens. However, very little is known about the innate immune responses, particularly the role of flagellin, in the induction of innate immunity triggered by recombinant attenuatedSalmonellain chickens. In the present report, we describe twoSalmonella entericaserovar Typhimurium vaccine strains, wild-type (WT) or flagellin-deficient (flhD)Salmonella, both expressing the fusion protein (F) gene of Newcastle disease virus. We examined the bacterial load and spatiotemporal kinetics of expression of inflammatory cytokine, chemokine, and Toll-like receptor 5 (TLR5) genes in the cecum, spleen, liver, and heterophils following oral immunization of chickens with the twoSalmonellastrains. TheflhDmutant exhibited an enhanced ability to establish systemic infection compared to the WT. In contrast, the WT strain induced higher levels of interleukin-1β (IL-1β), CXCLi2, and TLR5 mRNAs in cecum, the spleen, and the heterophils than theflhDmutant at different times postinfection. Collectively, the present data reveal a fundamental role of flagellin in the innate immune responses induced by recombinant attenuatedSalmonellavaccines in chickens that should be considered for the rational design of novel vaccines for poultry.

scholarly journals Innate Immune Responses to Systemic Acinetobacter baumannii Infection in Mice: Neutrophils, but Not Interleukin-17, Mediate Host Resistance

2011 ◽  
Vol 79 (8) ◽  
pp. 3317-3327 ◽  
Author(s):  
Jessica M. Breslow ◽  
Joseph J. Meissler ◽  
Rebecca R. Hartzell ◽  
Phillip B. Spence ◽  
Allan Truant ◽  
...  
Keyword(s):  
Immune Responses ◽  
Acinetobacter Baumannii ◽  
Systemic Infection ◽  
Innate Immune ◽  
Mouse Strains ◽  
Multiple Drug ◽  
Interleukin 17 ◽  
Innate Immune Responses ◽  
Bacterial Strains ◽  
Content Type

ABSTRACTAcinetobacter baumanniiis a nosocomial pathogen with a high prevalence of multiple-drug-resistant strains, causing pneumonia and sepsis. The current studies further develop a systemic mouse model of this infection and characterize selected innate immune responses to the organism. Five clinical isolates, with various degrees of antibiotic resistance, were assessed for virulence in two mouse strains, and between male and female mice, using intraperitoneal infection. A nearly 1,000-fold difference in virulence was found between bacterial strains, but no significant differences between sexes or mouse strains were observed. It was found that microbes disseminated rapidly from the peritoneal cavity to the lung and spleen, where they replicated. A persistent septic state was observed. The infection progressed rapidly, with mortality between 36 and 48 h. Depletion of neutrophils with antibody to Ly-6G decreased mean time to death and increased mortality. Interleukin-17 (IL-17) promotes the response of neutrophils by inducing production of the chemokine keratinocyte-derived chemoattractant (KC/CXCL1), the mouse homolog of human IL-8.Acinetobacterinfection resulted in biphasic increases in both IL-17 and KC/CXCL1. Depletion of neither IL-17 nor KC/CXCL1, using specific antibodies, resulted in a difference in bacterial burdens in organs of infected mice at 10 h postinfection. Comparison of bacterial burdens between IL-17a−/−and wild-type mice confirmed that the absence of this cytokine did not sensitize mice toAcinetobacterinfection. These studies definitely demonstrate the importance of neutrophils in resistance to systemicAcinetobacterinfection. However, neither IL-17 nor KC/CXCL1 alone is required for effective host defense to systemic infection with this organism.

scholarly journals Infection triggers tumor regression through activation of innate immunity in Drosophila

2019 ◽  
Author(s):  
Camille Jacqueline ◽  
Jean-Philippe Parvy ◽  
Dominique Faugère ◽  
François Renaud ◽  
Dorothée Missé ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Size ◽  
Bacterial Infections ◽  
Tumor Regression ◽  
Acute Infection ◽  
Innate Immune ◽  
Immune Gene ◽  
Infectious Agents ◽  
Innate Immune Responses

AbstractThe pioneering work of Dr. William Coley has shown that infections can stimulate the immune system and improve tumor growth control. However, the immune mechanisms responsible for the protective role of infectious agents have still not been identified. Here, we investigated the role of innate immune pathways in tumor regression by performing experimental infections in genetically modified Drosophila that develop invasive neoplastic tumors. After quantifying tumor size, through image processing, and immune gene expression with transcriptomic analyses, we analyzed the link between tumor size and pathogen-induced immune responses thanks to a combination of statistical and mathematical modeling. Drosophila larvae infected with a naturally-occurring bacterium showed a smaller tumor size compared to controls and fungus-infected larvae, thanks to an increase expression of Imd and Toll pathways. Our mathematical model reinforces this idea by showing that repeated acute infection could results in an even higher decrease in tumor size. Thus, our study suggests that infectious agents can induce tumor regression through the alteration of innate immune responses. This phenomenon, currently neglected in oncology, could have major implications for the elaboration of new preventive and immunotherapeutic strategies.One Sentence SummaryBacterial infections can decrease cancer cell accumulation through stimulation of innate immune responses.

Sign in / Sign up

Export Citation Format

Share Document